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Colonoscopy
Editors: Jerome Waye, Christopher Williams & Douglas Rex
4. Difficult polypectomy
U. Seitz, S. Bohnacker, S. Seewald, F. Thonke, N. Soehendra & J. Waye
Synopsis 
This chapter describes various techniques that can be employed to assist in the removal of colon polyps that are considered
to be large or 'difficult.' Size alone is only one of the features that may cause some hesitation in making the decision to attempt polyp removal. Other
factors that are related to the perceived level of difficulty are polyps that are flat and only slightly elevated above the
mucosal surface, location on a wall of the colon that is not accessible to the snare, a polyp in a segment of severe diverticular
disease or wrapped around a fold in clam-shell fashion. A polyp situated behind a fold can be difficult to approach, and those
in the cecum hidden behind the ileocecal valve present a special challenge for resection. These and other problems will be
addressed in this chapter as will the localization of lesions or polypectomy sites for future surgery (in the case of malignant
polyps) or for reevaluation following total or incomplete polyp removal. The impossible polyp is one which the endoscopist
feels cannot be removed. The feeling of futility when faced with such a polyp is directly dependent on the training, experience,
and courage of the endoscopist. What may be 'impossible' for one endoscopist may be a relatively 'routine' polypectomy for another. In general, there are three criteria that make a polyp 'impossible', and when the three occur in the same lesion, then the polyp may be 'really impossible'. The three factors which by themselves or in combination with others may place the polyp in an 'impossible' category are size, location of the polyp, and configuration. Factors suggesting difficulty in polypectomy 
Polyp size 
It is fortunate that polyps over three centimetres in diameter are not commonly found during colonoscopy. During the last
30 years, only few publications [18] have reported on endoscopic removal of large colorectal polyps (Fig. 1). Christie et al. [3] found in 1977 that only 58% of colorectal polyps measuring 2060 mm were amenable to endoscopic polypectomy. Bedogni et al. [9] reported in 1986 that in their experience 75% of colorectal polyps larger than 30 mm were endoscopically removable (66% of the removed polyps were sessile). Lower malignancy rates of less than 15% in large
colorectal polyps have been reported irrespective of their macroscopic and histologic growth pattern [2,10].
Malignant potential 
When large sessile polyps are identified, several decisions will impact upon the probability of its removal. The first factor
to consider is whether the polyp is benign or malignant. A question that arises is whether to perform a biopsy and then bring
the patient back for polypectomy based on the subsequent results of biopsy or to depend on the visual impression of whether
the polyp is benign.
There are no studies on the visual criteria which can be applied to a polyp to determine the presence of malignancy, however,
endoscopists in a tertiary referral center in Hamburg, Germany [2] have stated that a benign polyp does not have any of the following features: ulceration, induration, or friability. Japanese
endoscopists [6] who endeavored to remove large polyps noted that large flat polyps were usually benign, and that invasive carcinoma was only
seen in elevated sessile polyps.
These visual characteristics may not always be accurate, but biopsies are notoriously erroneous for the diagnosis of invasive
carcinoma within a polyp because the depth of tissue obtained is usually limited and because high-grade dysplasia on biopsy
(which used to be called non-invasive carcinoma or carcinoma in situ) is histologically identical to invasive carcinoma.
In addition, the amount of tissue sampled by biopsying a large polyp represents only a fragment of the total polyp volume
submitted for histopathology. Most colonoscopists base the decision as to whether a large polyp is benign or malignant on
the visual impression when it is identified.
If the assessment is that the polyp is benign, the decision for removal should be based on other visual criteria; if it looks
like it can be removed, an attempt should be made to resect it (Fig. 2).
There is a general reluctance among endoscopists to remove large polyps because of the possibility of invasive carcinoma.
One report stated a 40% incidence of invasive carcinoma in large polyps, but this finding was based on the pathologist's finding
of carcinoma in surgical specimens that were sent to the pathology laboratory, not polyps which were removed endoscopically
[11]. Endoscopically resected polyps, which meet the visual criteria of being benign, will actually have an incidence of about
1015% of invasive malignancy [2,6,9,10].
Configuration 
Assuming the polyp appears to be benign macroscopically, the average endoscopist (as opposed to the expert) will have greater
difficulty if any of three features [12] are present.
- The polyp occupies more than one-third of the circumference of the colon wall.
- The polyp crosses over two interhaustral septae.
- The polyp encircles and actually involves the base of the appendix.
More than one-third of the circumference 
The polyp which extends more than one-third the circumference of the colon wall will create a large mucosal defect if it is
removed. It is possible that polyps of this size could be removed by an expert endoscopist (Fig. 3), but even the expert may elect to send such a patient for surgical resection rather than face the possibility of multiple
colonoscopic examinations, particularly if the colonoscopic approach to the polyp was extremely difficult and demanding.
Polyps crossing two haustral septae 
Polyps that cross over two interhaustral septae present another problem in their total removal, since it may be almost impossible
to remove the entire polyp, especially the portion that lies in the valley between two interhaustral septae.
Polyps involving the appendiceal orifice 
Polyps that involve the appendiceal orifice may extend into the appendix, and, although this phenomenon is rare, total removal
of this type of polyp is problematic (Fig. 4).
Bleeding risk 
Large pedunculated polyps have a large nutrient artery, and may bleed during or after polypectomy. Injection of epinephrine
into the stalk may decrease the risk of bleeding. Other measures are application of endoloops; or a technique of using one
disposable snare to cut off the blood supply and another to perform the resection [13,14](Fig. 5).
Practice issues for difficult polyps 
Risks and consent 
When the decision is made by the endoscopist to attempt removal of large polyps, it is necessary to obtain the patient's agreement
with repeated endoscopy sessions and follow-up endoscopies. Complete resection of large sessile polyps may require several
sessions, and since high rates of local recurrencies are reported [4,8,9], it is mandatory to confirm complete removal by follow-up examinations.
Much of the reluctance to remove large polyps is related to the fear of complications. The actual incidence of perforation
in removal of large polyps is low, with 2 series [2,6] of large polypectomies reporting that no patients required surgical intervention, there were no perforations, and when bleeding
during polypectomy occurred in 10% and 24% [2] of patients it was successfully handled. The published rate of complications indicates that bleeding occurs in 1.4% of polypectomies
and perforation in 0.3% of patients [5].
Ambulatory or in-patient polypectomy 
Most diagnostic colonoscopies are performed on an ambulatory basis. When a large polyp is encountered that meets the criteria
for removal, the endoscopist must decide whether the patient should be admitted to the hospital, or, to do the polypectomy
in a hospital out-patient setting, or whether it is safe to perform the procedure in an office facility remote from a hospital?
Literature supports the safety of ambulatory polypectomy [15], and only 1 of 170 patients who had large polyps removed required immediate hospitalization for suspected perforation [2].
Which colonoscope for difficult polyps? 
For difficult polypectomy, a therapeutic colonoscope with a 4.2-mm working channel and an additional channel for a water pump
is recommended. This allows for sufficient simultaneous suction during the procedure which is particularly helpful in the
face of severe bleeding. An additional small-bore channel connected to a water pump provides a strong water jet for cleansing
the mucosa surface, e.g. in case of oozing during EMR or piecemeal resection. Many endoscopists use a standard colonoscope
for removal of large polyps.
Sometimes a thinner endoscope is helpful 
A pediatric colonoscope is useful, but not generally available. A standard upper intestinal gastroscope has been demonstrated
to be of benefit [35]. The major attributes of the gastroscope is that it has a tighter bending radius of the tip than does a colonoscope and the
tip beyond the bending portion is shorter in length. This will frequently allow easy snare positioning in the same location
where the colonoscope was both cumbersome and difficult. There is a growing awareness among endoscopists that gastroscopes
can easily and readily be used in the colon to intubate difficult and narrowed segments, to be passed through strictures,
and to render a previously inaccessible polyp more readily manageable. The upper intestinal endoscope can be of use even in
the rectum, where it may not be possible to snare a polyp on the proximal surface of one of the rectal valves. In this circumstance,
the bending section of the colonoscope may be too long to permit a tight turn, whereas a gastroscope with its greater tip
deflection capability and shorter 'nose' (or straight portion beyond the bending section) may permit easy visualization and removal of polyps.
Which snare?  Types of snares 
For resection of difficult polyps there is probably no significant difference between snares made of braided and monofilament
wire. A braided wire creates more coagulation effect than a monofilament wire. Bleeding may be less frequent with braided
wire, but it may carry a higher risk of perforation due to greater thermal penetration depth. In our experience, a monofilament
snare made of 0.5 mm steel wire is stiffer and provides greater stability for ensnaring flat polyps (Fig. 6). The standard Erlangen polypectomy snare (Grosse Co., Daldorf, Germany) is 5 × 3 cm of size. In a narrowed bowel lumen such as encountered in diverticulosis, a smaller floppy snare made of braided wire may
be useful.
Use of the mini snare 
Even after total colonoscopy has been performed and the colonoscope has been straightened, there may still be difficulty in
the sigmoid colon when attempting to capture a polyp because of narrowing by diverticula and thickened hypertrophic folds.
There are two maneuvers which may permit easier endoscopic polypectomy.
The first is to use a mini snare, which will allow a full extension of the snare within a short segment of the bowel. The
standard regular-sized polypectomy snare may not be able to capture a small polyp in a difficult and 'tight' location where there is not sufficient distance for the wire loop to open sufficiently wide to be placed over a polyp.
A problem with the standard snare is that it must be completely extended to its full length of 6 cm in order for the loop to completely expand. During colonoscopy, it often occurs that the wire loop can only be extended
a few centimeters beyond the scope because of a tight bend or because the tip of the loop impacts on an adjacent wall of the
colon. When the snare loop cannot be fully extended, the two partially open parallel wires may not sufficiently spread apart
to enable polyp capture. In this circumstance, a 'mini' snare 3 cm in length and 1.0 cm in width [33,34] is extremely valuable. This snare will open fully when extended only 3 cm beyond the sheath making it useful in areas where multiple bends are present (such as in the sigmoid narrowed with diverticulosis),
or when polyps are located in the depth between intrahaustral folds. Since the vast majority of colon polyps are less than
1.0 cm in diameter, they are within the limits of this mini-snare.
Submucosal injection for polypectomy (SIP) 
The submucosal injection technique is often used for removal of large sessile adenomas [16,17]. Deyhle et al. first performed submucosal injection to raise flat mucosal lesions facilitating ensnaring in 1973. Saline or epinephrine
solution (1 : 20 000) is injected from the margins of the polyp. Submucosal injection may be useful to lift parts of the polyp located in the
appendiceal orifice or behind a haustral fold. However, submucosal injection even with large amounts of saline solution may
not avoid perforation, if too large pieces of polyp are ensnared and resected [18]. Diluted epinephrine solution is used to prevent bleeding during polypectomy. However, a possible drawback of this precaution
may be delayed bleeding due to the short-lasting vasoconstrictive effect of epinephrine.
Endoscopic mucosal resection (EMR) using a double-channel endoscope was introduced by Tada et al. in 1993 [19] to remove large sessile and flat polyps. The lesion is lifted by using a forceps to enable ensnaring ('lift and cut' technique). Several modifications of EMR technique have been introduced in the management of early cancer of the stomach
and esophagus [20].
In the colon and rectum, EMR is widely performed using the simple snare resection technique. The colon wall is 1.52.2 mm in total thickness, and thermal damage to deep layers of the colon is frequently encountered [21]. Injection of fluid into the submucosa beneath the polyp will increase the distance between the base of the polyp and the
serosa. When current is then applied via a polypectomy snare, the lesion can be more safely removed because of a large submucosal
'cushion' of fluid which lessens the likelihood of thermal injury to the serosal surface.
It is permissible to remove a much larger piece with this technique than one would ordinarily resect when in the right colon
without a 'cushion' of fluid. The pieces should probably not be larger than 2 cm in diameter [6]. With the fluid as protection against deep thermal tissue injury, it is possible to fulgurate the base of the resection site
with devices such as a hot biopsy forceps, the tip of the snare, the argon plasma coagulator, or any other thermal device
which delivers heat to the residual polyp site.
Injection fluid 
The fluid, injected through a long and stiff sclerotherapy needle, may be saline (normal or hypertonic) [22], with or without methylene blue to enhance visualization and with or without epinephrine [23]. Most endoscopists use normal saline only. Hypertonic saline solution and epinephrine are used to retain the fluid at the
site for a longer period, but submucosal saline lasts for 1015 minutes, which is sufficient time for removal of most polyps. A viscous mucinous solution of 0.5% sodium hyaluronate has
been used (via a 21 gauge needle) to elevate large flat polyps for endoscopic mucosal resection [24]. This solution is isotonic and remains at the injection site longer than saline.
Further studies need to be performed to assess the practicality of various injection solutions. There is a theoretical advantage
to the injection of dilute epinephrine, to prevent bleeding at the time of polypectomy or to prevent delayed bleeding (Fig. 7). However, the incidence of immediate bleeding is low (1 out of 100 procedures) [25], and the long-term effect is nil because the vasoconstrictive action is measured in hours, not days.
Injection site 
The injection needle may be placed into the submucosa just at the edge of a polyp, or if the polyp is large and flat, multiple
injections may be given around the polyp or directly into the middle of the polyp. If a bleb does not form at the injection
site when 1 mL of fluid has been given, the needle should be withdrawn since the tip may have penetrated the wall and pierced the serosal
surface. When the needle is in the submucosal plane, continuous injection of saline will result in submucosal infiltration
of fluid. A large localized fluid collection is the desired endpoint, with marked elevation of the polyp.
When the tissues expand in response to fluid injection, the fluid is being deposited in the areolar tissue of the submucosal
layer since neither the mucosa, muscularis propria or the serosa will accept injected substance.
If the needle placement is too superficial, the fluid will leak out from the beveled edge and spill into the lumen. This spilling
is especially noticeable when a colored fluid is used, such as methylene blue or India ink. Multiple repeated needle placements
and attempts at injection may be required to locate the correct plane for polyp elevation. If possible, the approach by the
needle injection should be tangential and not perpendicular to the mucosal surface. Polyps up to 2 cm in diameter may be removed with one application of the snare, but larger polyps may require several transections in piecemeal
fashion [26].
Polyps behind folds 
When part of the polyp is either hidden from view behind a fold or wrapped around a fold in clamshell fashion, injection of
the part nearest to the colonoscope may elevate that portion, but can cause interference with polypectomy because the mound
of saline will block vision. The solution to this problem when the proximal edge of the polyp is hidden is to inject the far
side of the polyp. This is accomplished by passing the scope beyond the far edge of the polyp. While deflecting the tip toward
the polyp, the injection should be made into the normal mucosa just at or near the edge of the polyp (or into the proximal
edge of the polyp).
Injection into the wall on the far side of the polyp will raise that portion up on the fluid mound, rendering snare application
easier (Fig. 8). Depending on the polyp size, several injections may be required to elevate the polyp so that snare placement is more readily
accomplished. After the back portion of the polyp has been removed, then saline may be injected into the area closest to the
scope to assist in completing the polypectomy.
Injection volume 
When attempting SIP, there is not a specific volume of fluid which is used, but rather, the desired end point is a large submucosal
swelling beneath the polyp and adjacent portions of the mucosa. Elevation of the polyp may take 34 mL of saline given in several places, although some authors use up to 30 mL of fluid [6].
The non-lifting sign 
In general, malignant tumors should not be removed by the submucosal injection technique. If a polyp fails to elevate (the
'non-lifting sign') [27], it may be an indication of infiltration by cancer into the submucosa, with fixation by tumor limiting the expansion of the
submucosal layer [28]. Although deep or superficial needle placement may be the cause for failure to raise a bleb under a polyp, a submucosal bulging
or bleb on one side of a polyp in response to injection without any visible elevation of the tumor itself is a clue that there
is fixation into the submucosa. This phenomenon may also be caused by a prior attempt at polypectomy with healing and scarring
of the mucosa and submucosa, preventing their separation by fluid injection.
Tumor tracking 
There is a theoretic possibility that injection through a malignant tumor may cause tracking of cancer cells into and even
through the bowel wall. The risk of this happening is minimal, with experience gained from direct percutaneous needle aspiration
of malignant tumors in other sites throughout the body. In the latter instances, the risk of tumor tracking is 1 in 10 0001 in 20 000 cases [29].
Parenthetically, it seems that any tumor which can be elevated with submucosal injection of fluid may be totally removed by
endoscopic resection, even if invasive cancer is found on tissue examination. The ability to elevate a tumor indicates that
there is only a limited degree of fixation to the submucosal layer, with the possibility of complete removal.
Cap assisted polypectomy 
A suction cap may be attached to the colonoscope tip, and a preloaded snare can be placed at the mouth of the cap. Once the
polyp elevated with SIP has been aspirated into the cap, a sizable portion of the wall can be removed using coagulation current.
Caution is urged for using this technique above the peritoneal reflection [30]. Endoluminal full-thickness resection using a rigid instrument was introduced by Buess et al. to remove sessile and/or malignant polyps in the rectum (Buess et al. 1984) [31]. This technique may offer a better alternative to endoscopic piecemeal resection or resective surgery in selected cases.
However, it does not allow for lymphadenectomy, and has therefore a limited use in malignant lesions that cannot be treated
endoscopically. Furthermore, it is questionable whether a recently introduced system will allow polypectomy in the proximal
colon.
Polyp resection technique 
Stop at the line 
When complete visualization is not possible as the loop is being closed, the assistant should close until resistance is met,
or, if no closure sensation, then stop at the line on the snare sheath. Once closed, the catheter sheath should be jiggled
to and fro at the biopsy port while observing the colon walls around the polyp. If extraneous portions of the mucosa are not
caught, the polyp will be seen to move independently of the surrounding colon walls as the sheath is jiggled. If the polyp
and the surrounding wall move simultaneously, there is a strong probability that a portion of adjacent mucosa has been captured
within the snare loop. Complete removal of the snare or partially opening the loop for repositioning is advisable before application
of electrocautery current. Transection of a large fragment of inadvertently captured normal mucosa is not a desirable outcome
of polypectomy and may lead to perforation. If extra tissue is captured, there is no assurance that it will only consist of
mucosa, for submucosa may also be entrapped, and when electrocautery current is applied, a deep burn may result.
Piecemeal polypectomy 
When removing a sessile polyp, the characteristic whitening at the site of wire placement when electrocautery current is applied
often cannot be observed because the wire is embedded in the polyp. After a few seconds of current, the wire snare should
be slowly closed until separation occurs. During piecemeal polypectomy, the next placement of the snare may be immediately
adjacent to the first, with the edge of the wire positioned into the denuded area just created by removal of the previous
piece (Fig. 9). In this fashion, multiple portions can be sequentially resected in an orderly fashion, with removal of each succeeding
piece being facilitated by its predecessor. Several applications may be required, removing fragments until satisfactory polypectomy
is achieved [7,32]. The polyp fragments may be removed by suction into a trap if they are small or retrieved with a Roth basket or, less effectively,
with a dormia basket or a tripod grasper. One or two fragments may be captured in a snare loop for removal.
The fulcrum technique may be used for the endoscopic treatment of laterally spreading polyps. The tip of the opened snare
is impacted against the colonic wall behind the polyp. By keeping the tip fixed, slightly advancing the snare, and bending
the endoscope tip to left or right the snare is pivoted to either side (Figs 10 and 11). If the tip of the opened snare is placed in front of the polyp, it can be flexed backwards along its long axis by advancing
the snare and the tip of the endoscope (Fig. 12). To prevent perforation, the wire loop should be pressed flat against the bowel wall to ensnare the mucosal and submucosal
layers only.
Positioning the polyp 
Whenever a polyp is to be removed, snare placement is facilitated by rotation of the colonoscope to bring the polyp to the
5 o'clock position. Rotation of the scope is necessary to reposition the instrument tip in relation to the polyp.
Rotation of the scope may be difficult during intubation when the instrument shaft has loops and bends. Advantageous positioning
may be best accomplished when the colonoscope shaft is straight, because a straight instrument transmits torque to the tip,
whereas a loop in the shaft tends to absorb rotational motions applied to the scope. It is often difficult to capture a sigmoid
polyp during intubation, when the obligatory sigmoid loop is present. It may not be possible to straighten the scope in the
sigmoid during the intubation phase because rotation and loop withdrawal often results in losing the scope's position. With
a loop in the scope, the dial controls may no longer work effectively to turn the instrument tip because the cables which
transmit motion are maximally stretched by the loop.
These two negative forces, the inability to torque effectively and the loss of cable-controlled tip deflection, combine to
create a difficult situation when attempting to maneuver the snare into position around a polyp. Snare placement can be made
considerably easier by passing the scope far beyond the polyp, even to the cecum (and thus visualize the rest of the colon)
and attempt capture during the withdrawal phase of the examination. As the scope is withdrawn, the loops are removed and the
polyp which proved difficult to position during intubation may be quite easily ensnared because both torque and tip deflection
are responsive when the shaft is straight.
Clamshell polyps 
Large sessile polyps wrapped around a fold in a 'clamshell' fashion usually permit the distal portion to be readily removed, but resection of the proximal portion on the far side of
the fold may be considerably more difficult. This type of polyp is often located in the right colon and should be removed
in piecemeal fashion (Fig. 13).
The piecemeal technique usually requires rotation of the colonoscope to place the polyp at the 56 o'clock position. Although it would be ideal to resect the total polyp at one session, it may only be possible to remove
the portion nearest to the scope, leaving some of the polyp on the far side of the fold for an interval resection. Subsequent
scarring may flatten the polypectomy site, bringing the residual polyp into a favorable location for subsequent polypectomy.
Often, an injection of fluid (SIP) into the mucosa on the far side of the polyp will facilitate its removal, as previously
described.
If it is elected to attempt total polypectomy at the first session, the stiffness of the plastic snare catheter can be used
as a probe. After endoscopic transection of the portion closest to the scope, and with the loop extended, the tip of the catheter
can be positioned on the ridge of the fold in the polypectomy site where a portion of the polyp has just been removed. By
a combination of torque and rotation of the large control knob, downward pressure on the ridge at the site of the polypectomy
divot will often depress it sufficiently so that a portion of the residual adenoma will extend into the loop permitting capture
under direct vision (Fig. 14).
Several repeated snare applications and transections of this type will usually result in complete polypectomy. The tip of
the instrument must be close to the polypectomy site for this technique to be effective, since the plastic polypectomy sheath
becomes quite flexible when it is extended more than a few centimeters beyond the colonoscope. The sheath, with its tip barely
protruded from the faceplate of the scope, is stiff and will depress a fold when torque or tip deflection is applied to the
colonoscope shaft. A stiff monofilament snare may be used to flatten the fold exposing the entire polyp. Pushing on a fresh
polypectomy site in this manner is not associated with any adverse results.
Retroversion 
An alternative technique for removal of a polyp located on the far side of a fold is to perform a U-turn maneuver. With standard
instruments, this can only be accomplished in the cecum, ascending colon, and sometimes in the transverse colon although it
is somewhat easier with pediatric colonoscopes. It is difficult but not impossible to resect a polyp in a U-turn mode because
the tip deflection responses are opposite to those usually expected (Fig. 15).
Flat polyps 
In spite of the knowledge and skill of modern endoscopists, not all colon polyps can be successfully removed with a colonoscope.
Among these are carpet-like polyps which extend over several centimeters. An attempt can be made to fulgurate the surface
of such polyps with the shank of the monopolar biopsy forceps, a BICAP probe, a laser, or the argon plasma coagulator.
A helpful maneuver to be considered when the lesion appears too flat to capture with the snare loop is to aspirate air from
the colon with the snare device in place. This will collapse the distended colon, causing a decrease in the circumference
of the colon wall and as that occurs, the polyp flattened against the stretched wall, will become thicker and more elevated,
rendering capture relatively easy so that piecemeal type resection may be performed.
Alternate possibilities include submucosal injection of fluid to elevate the polyp for safer transection and use of a two-channel
colonoscope where a forceps can be passed through one channel to grasp the polyp over which the opened snare has been positioned.
Once the forceps lifts up the polyp, the snare is tightened to capture the polyp.
Residual fragments of adenoma after polypectomy 
Often the base of a large polyp which was resected in piecemeal fashion has some residual adenomatous tissue at the edge or
in the middle of the polypectomy site. If residual tissue is seen at the base, there will be adenomatous tissue at that site
on follow-up colonoscopy. The site of polyp resection heals concentrically, from the edges toward the center, so that usually
only one polypoid excrescence will be present upon complete healing of the site, whether or not several small islands of adenoma
remained at the periphery of the initial resection base. If the polypectomy was adequate, the residual polyp will be smaller
than the original size of the polyp, and can be easily removed.
The application of thermal energy to the fragments of adenoma remaining at the base and edges of a fresh polypectomy site
can reduce the incidence of residual polyp (Fig. 16). This has been studied with the argon plasma coagulator (APC), with reduction of adenoma on follow-up from 100% to 50% when
residual tissue at the fresh base is destroyed [36,37].
Judging and marking the location of lesion 
There are several reasons to mark an area of the colon for future localization. Most of the time, the endoscopist desires
to have a precise identification of the site where a polyp was removed. When large polyps are resected in piecemeal fashion,
even though the endoscopist considered that it was totally removed, there is a strong possibility that residual adenoma will
be present at a follow-up examination. It may be difficult to find the exact place where a polyp was removed, as the initial
placement of the site was wrong, the scar is behind a fold, or the residual is small. Of equal importance is the knowledge
that the polyp was indeed completely resected at the original session, and the site can be declared free of residual adenoma.
Now that laparoscopic-assisted surgical colonic resection is becoming as well accepted as primary colonoscopy, there is even
greater urgency to have precise lesion location, since the laparoscopist does not have the capability of palpating the colon
between the fingers at exploratory laparotomy [38]. For the laparoscopist, it is of great importance to have an easily visible marker which can be seen through the telescopic
lens of the laparoscope. It is not acceptable for the endoscopist to state that 'a lesion is in the transverse colon', since a more specific localization is needed to avoid a subsequent open surgery to find the lesion.
Even under circumstances when open laparotomy is to be performed, site identification becomes necessary when a specific portion
of the large bowel requires resection and the lesion may not be readily apparent by visual or palpatory exploration. Following
endoscopic removal of a malignant adenoma, the site may heal completely in eight weeks, and a locator mark may assist both
the surgeon and the pathologist in identifying the place where the lesion had been.
Location by depth of insertion 
Localization by measurement of centimeters of instrument introduced into the rectum is an extremely poor method for tip localization
[39]. During introduction of the instrument, when loops are common, it is possible to advance the full length of a long colonoscope
(180 cm) into the rectum, yet the tip may still be at the sigmoid/descending colon junction [40]. On the other hand, it is possible, by repositioning the instrument, removal of loops, and straightening, to reach the cecum
in that same patient with a total length of only 60 cm of instrument. The actual number of centimeters inserted may bear no relationship with the actual tip location within the
colon [41].
A report from a previous examiner that 'a polyp was found at 100cm' is meaningless for surgical localization. With the current knowledge of intraluminal landmarksthe splenic flexure, transverse colon, hepatic flexureit is much better to identify the approximate area of the lesion. During withdrawal, there is usually a good correlation between
length of scope inserted and tip localization since the loops are removed and the instrument is straightened. It is usual,
on withdrawal, to have the splenic flexure at 4050 cm and the upper sigmoid at 3035 cm. Because of sigmoid looping, shaft measurements during withdrawal are not usually helpful until the splenic flexure has
been reached.
Endoscopic landmarks 
Landmarks are notoriously imprecise for exact localization of areas between the rectum and cecum. Even the most experienced
colonoscopists may err in their estimate of tip location [38,40,42]. Indeed, in a large tortuous sigmoid colon, it may be difficult to localize a lesion to even the mid- or upper sigmoid colon.
Similarly, a lesion estimated by the endoscopist to be near the splenic flexure may be under the diaphragm, could be either
proximal or distal to the flexure, or may even be actually located at the sigmoid descending colon junction. Precise location
may be impossible because of tortuosity and multiple bends in that area of the colon. The only invariable localizing landmarks
are when a lesion is located within 15 cm of the anus, there is no doubt that it is close to or in the rectum, and a lesion near the endoscopically identified ileocecal
valve can be easily found by the surgeon. The problem in the latter case revolves about the endoscopist's ability to recognize
beyond a doubt that the cecum was indeed reached.
Clipping 
Clips may be placed through the colonoscope and onto the mucosa at any location. These will assist in radiographic or ultrasonographic
location of the marked segment. However, clips tend to fall off at an average of approximately 10 days [43], with some falling off earlier and some maintaining their attachment for longer intervals. Although it has been suggested
that clips may be a helpful marker for surgical localization, it has been found that the clip devices are quite small to be
palpated easily. In addition, the surgeon cannot be assured that a palpable clip had not been spontaneously detached just
prior to surgery and is at some distance from the original placement during endoscopy. If, indeed, a surgeon palpates a clip
in the sigmoid colon and resects that segment, it is possible that the clip actually had been placed at a location near the
splenic flexure, had become detached, and migrated distally. A report of eight patients with prelaparoscopic clip placement
by colonoscopy stated that intraoperative ultrasound readily located the marked areas for surgical resection [44].
Marker injections into the colon wall 
The ideal method for lesion localization is to have an easily identifiable marker which will immediately draw the attention
of the surgeon or endoscopist [42]. This can be achieved with injection of dye solutions. An experimental study demonstrated that, of eight different dyes injected
into the colon wall in experimental animals, only two persisted for more than 24 hours [53]. These were indocyanine green and India ink. The indocyanine green was visible up to seven days after injection, and it is
known that India ink is a permanent marker which lasts for the life of the patient by virtue of submucosal injection of carbon
particles. Other dyes, such as methylene blue, indigo carmine, toluidine blue, lymphazurine, hematoxylin, and eosin, all were
absorbed within 24 hours, leaving no residual stain at the injection site. Indocyanine green is approved by the FDA for human use, but India
ink has not been so approved. A new surgical marker has been FDA approved, and consists of pure carbon in suspension. It is
marketed as a prediluted sterile compound in preloaded syringe [54].
Indocyanine green 
Indocyanine green is not associated with any significant tissue reaction, and is relatively non-toxic, but ulceration of the
injection sites have been reported in an animal model [53,55]. Clinical experience with indocyanine green tattoo in 12 patients demonstrated that the dye was easily visualized on the
serosal surface of the colon at surgery within 36 hours following injection [56] and may remain visible for up to seven days [53]. Animal experimental models have shown that the dye was not visible after one day [55] or lasted up to two weeks [57]. The problem with a marker having such a relatively short visible span is that the decision to operate after removal of a
malignant polyp may require a few weeks, with slide reviews and multiple consultations. An injection at the time of polypectomy
will have disappeared whereas the site itself may become more difficult to localize with the passage of time.
India ink 
Most experience with dye injection technique has been accumulated with India ink as a permanent marker [58,59]. The stain lasts for at least 10 years with no diminution in intensity at that duration. A permanent marker may be worthwhile
for several reasons. A lesion requiring surgery may be injected and, for clinical reasons, surgery may be postponed for several
weeks at which time a vital dye such as indocyanine green will have been absorbed, leaving the operating surgeon with no visible
evidence of its having been injected. Sometimes it is desirable to mark the site of a resected polyp for subsequent endoscopic
localization when it is anticipated that the area will be difficult to find on a follow-up examination, especially when the
lesion is located around a fold or behind a haustral septum.
A stain with a permanent marker such as India ink will draw immediate attention to the site, enabling a more accurate and
complete assessment. For the surgeon, a locator stain will aid immeasurably the efforts to seek and resect an area of the
bowel containing the site of the lesion. When the lesion is relatively small, such as a flat cancer or a previously endoscopically
resected malignant polyp which requires surgical resection, the site may not be evident from the serosal surface and may not
even be palpable. If the area to be resected is in a redundant sigmoid colon or near the splenic flexure, it may be impossible
to locate by either visual means or by palpation. Occasionally, even large lesions may not be palpable by the surgeon if they
are soft and compressible [60]. As previously mentioned, visible marking can assist in precise surgical intervention for laparoscopic-assisted colon resections,
or clips may be detected by an ultrasound probe.
There have been reported complications with India ink injection, but clinical symptoms resulting from the injection are relatively
rare [61,62]. Tissue inflammation has been reported in an animal model [55]. The complications may in part be related to the wide variety of organic and inorganic compounds contained in the ink solution,
such as carriers, stabilizers, binders, and fungicides [63]. It is possible that the toxic properties of India ink may be partially ameliorated by marked dilution of the ink. Ink diluted
to 1 : 100 with saline produces as dark a spectrophotometric pattern as undiluted India ink, and in clinical tests, the tattoo made
by 1 : 100 diluted India ink is readily visible by the endoscopist and by the operating surgeon. A small volume injection (0.5 mL) may increase the safety of the procedure [55,64].
India ink is black drawing ink made with carbon particles. Permanent fountain pen ink is not an acceptable substitute. India
ink is available from any stationery store, although it is supplied for medical use in non-sterile form as a stain to enhance
the diagnosis of crytococcosis in the cerebrospinal fluid. The India ink may be sterilized in an autoclave following dilution
or can be rendered bacteriologically sterile by passing the diluted solution through a 0.22 micron Millipore filter which
is interposed between the syringe containing the dilute solution of India ink and the injection needle [65]. The preparation of India ink, prior to injecting the carbon particles into the submucosa is not required of a new compound
of sterile micronized carbon particles [54].
A standard sclerotherapy needle is utilized of sufficient length to traverse the accessory channel of a 168-cm colonoscope,
and stiff enough so that the plastic sheath will not crinkle up as it is being forced through the biopsy port when the tip
of the instrument is deep in the colon and the colonoscope shaft has several convolutions and loops. Ideally, the needle should
enter the mucosa at an angle to permit injections into the submucosa, rather than to have the needle pierce the bowel wall.
The edges of intrahaustral folds should be targeted (Fig. 17). If during an injection a submucosal bleb is not immediately seen, the needle should be pulled back slightly, since the
needle tip may have penetrated the full thickness of the wall and the ink may be squirting into the peritoneal cavity. An
intracavity injection is not a clinical problem [45,46], but can scatter black carbon particles around the abdominal cavity, which may be somewhat disconcerting for the surgeon.
A prior submucosal injection of saline may aid the colonoscopist in depositing the carbon suspension in that layer, without
risk of injecting either deep or superficial (Fig. 18) [66].
Since the colonoscopist cannot know which portion of the bowel is the superior aspect, multiple injections should be made
circumferentially in the wall around a lesion to prevent a single injection site from being located in a 'sanctuary' site, hidden from the surgeon as the abdomen is opened with the patient lying supine [67]. Each injection should be of sufficient volume to raise a bluish-black bleb within the submucosa at the injection site. The
injection volume may vary from 0.1 to 0.5 mL. If injections are made a few centimeters from the lesion, the surgeon should be informed whether the injections are proximal
or distal to the site. With the proper dilution of India ink, endoscopic visualization is still possible should some of the
ink spill into the lumen, whereas, with the more concentrated solutions, the endoscopic picture becomes totally black when
ink covers the bowel walls [45].
Most endoscopists who use India ink to mark colonic lesions do not prescribe antibiotics prior to its use, although it has
been suggested that prophylactic antibiotics be given before injections of indocyanine green [56].
Injection of carbon particles provides a permanent marker, with endoscopic visualization of the tattoo site being possible
in every case on follow up examination without diminution in color up to an interval of 10 years following initial injection
(Fig. 19). Several reports have attested as to its safety as well as its efficacy [61,68,69].
Intraoperative colonoscopy 
It is possible to localize the site of a tumor, or a resected polypectomy site, by performing intraoperative colonoscopy [50,51]. This technique has been avoided by most endoscopists because of the need to perform an endoscopic examination in the operating
room with all the constraints of positioning the patient, handling the scope, and trying to use maneuvers such as torque and
straightening techniques with the abdomen open. The amount of air insufflated for colonoscopy can create problems with surgical
techniques once the endoscopist has completed the necessary localization. Because the site of a polypectomy may heal within
a few weeks, there is a possibility that a polypectomy site may not be seen during an intraoperative endoscopy. Lesion identification
can also be accomplished by colonoscopy and submucosal injection of radioactive labeled albumin microaggregates [52] just prior to surgery. The surgeon can localize the precise area with detection by a gamma probe during laparotomy or laparoscopy.
Radiological methods of localization  Barium enema 
The barium enema is still an acceptable method for determining the location of polyps or cancers [41], but small lesions may not be readily identified on the barium enema X-ray examination. Certainly, if a malignant polyp were
endoscopically resected, it may be extremely difficult to then try to locate the area where the polyp was removed, since only
a small puckering may be present [41,45], or the site may be almost completely healed within three weeks.
During colonoscopy in a suite where radiographic imaging is possible, either fluoroscopy or an X-ray of the abdomen during
endoscopy may assist in locating the site of a lesion. Unfortunately, it may be difficult, with the instrument in a straightened
configuration, to state that the tip of the colonoscope is in the distal descending colon or in the mid-portion of a long
redundant sigmoid loop.
Magnetic imaging 
New methods of inductive sensing with a low-intensity magnetic field may aid in the moment-to-moment localization of the tip
of the fiberoptic colonoscope as it progresses through the colon. The magnetic sensors are attracted to electromagnets within
the sheath of the colonoscope (or on a wand-like device inserted into the biopsy channel) [46,47]. These methods have replaced such devices as metal detectors for localization of the instrument tip [48]. Unlike a fluoroscopic image which demonstrates both the scope and air in the colon as a contrast media, the electromagnetic
field method only shows the colonoscope itself, but is capable of a three-dimensional format. This technique may be of benefit
in localizing the site of a colonic tumor or polyp [49].
The extremely difficult colonoscopy 
If passage to the right colon has been arduous and prolonged, with the discovery of a large sessile polyp having a broad attachment
that would require several attempts at piecemeal polypectomy, the wisest approach may be to suggest surgical resection. The
riskbenefit ratio will depend on the location of the polyp: the right colon is somewhat thinner than the left, increasing the
risk of colonoscopic removal. Also there are some patients with limited physiological reserves, who may be unacceptable operative
risks.
The advent of laparoscopic-assisted partial colectomy may markedly change the attitude of adventurous colonoscopists who attempt
removal of large polyps, especially in the right colon [70]. The ease of laparoscopic resection may reduce the willingness of both the patient and the endoscopist to embark on the repetitive
number of colonoscopies required. Both the risks and benefits of an aggressive endoscopic approach will need to be reevaluated.
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