dissection for colorectal tumors - doiserbia · the oral side, and proceed with the dissection....

In the colorectal tumor, the lesions suitable for theendoscopic treatment are those with no lymph no-de metastasis such as adenomas, intramucosal ca-ncers, and minimally invasive submucosal cancer(invasion depth 1000 m, well and moderately dif-ferentiated type, no lymphovascular invasion).The new endoscopic technique, endoscopic sub-

mucosal dissection (ESD) enables en-bloc resection ofthe lesions regardless of their size and location. In order to perform ESD more easily, safely, and effi-ciently, we invented water jet short needle knives(Flush kni-fe). Emitting a jet of water from the tip of a sheath enablessubmucosal local injection with a knife itself wi-thoutreplacement of operative instruments, which leads toefficient treatment. Especially, Flush knife is very ef-fective for the lesions located at lower rectum and analcanal where there are many vessels. We tre-ated a to-tal of 361 colorectal lesions by ESD between June 2002and July 2007, and en-block complete resection ratewas 98.3 %. In 12 cases, "muscle retracting sign" wasrecognized. This sign is an index of the discontinuation of ESD,but it is impossible to diagnose preoperatively. Thepostoperative bleeding occurred in 0.8 % (3 cases: noblood transfusion is needed). The intraoperative perforation occurred in 1.9 % (6cases: 5 cases were treated conservatively, 1 case wastreated surgically) and the postoperative perforationoccurred in 1case (0.3%) treated surgically. ESD is theextremely effective treatment for the colorectal tumorsand also is possible to be performed safely with the ap-propriate choice of the devices and strategy for dissec-tion.

Key words: endoscopic submucosal dissection (ESD);Flush knife; colorectal tumors; muscleretracting sign

INTRODUCTION

The development of endoscopic submucosal dissection(ESD) enables en-block resection of the lesions which

were difficult to be removed by the conventional en-dos-copic mucosal resection (EMR). EMR is a so called

adva-nced polypectomy using a snare. On the other hand,we can say that ESD is endoscopic surgery because we in-cise the mucosal layer around the lesion and dissect thesubmucosal layer with endo knives. Theoretically, ESDena-bles en-block resection of a lesion regardless of itssize and location. However, ESD is associated with higherte-chnical difficulty, longer procedure time, and increasedrisk of complication. The risk of complication of colorec-tal ESD is thought to be much higher than gastric ESD be-cause of the thin wall and narrow lumen. Recently,colorectal ESD can be performed rather easy and surelywhen we choose the method that is appropriate to the ana-tomical characteristic. Above all, the rectum has compara-tively thick muscle layer and wide lumen, so it is rathereasy to approach by ESD. Moreover, the invasion by theoperation of the rectum is serious. Therefore, the rectumis the most proper location for the ESD. In this report, wedescribe an outline of the methods, treatment results, indi-cations and limitations of colorectal ESD.

PATIENTS/ MATERIALS AND METHODS

We introduced ESD from June 2002. In the colorectum,we assume the lesions larger than 20mm to be the indica-tion for ESD, and have resected 361 lesions (adenoma;118, mucosal cancer; 177, submucosal cancer; 66) by July2007.

THE SUITABLE LESIONS FOR THE ENDOSCOPICTREATMENT

The curability is the major point of indication of ESD;whether with or without lymphnode metastasis. ESD isthe local resection, so its objects are the lesions without

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The results and limitations of endoscopic submucosaldissection for colorectal tumors

T. Toyanaga1, M. Man-I1, D. Ivanov3,T. Sanuki1,Y. Morita2, H. Kutsumi2, H. Inokuchi2, T. Azuma2

1,2Department of Endoscopy and Gastroenterology, KobeUniversity Hospital, Kobe, Japan3Clinical Center of Vojvodina, Clinic for Abdominal,Endoscopic and Transplant Surgery, Novi Sad, Serbia

/STRU^NI RAD UDK 616.348/.35-006.04-089-072.1

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metastasis. In the Colorectum, these lesions are concretelyas below, 1) Adenomas 2) Intramucosal cancers 3) Mini-mally invasive submucosal cancers (invasion depth1000m, well and modelately differentiated type, no lym-phovascular invasion) 1).

THE DEVICES FOR ESD AND THEIR CHARAC-TERISTIC

The development of the devices has enabled us to per-form ESD. Especially, the development of electro surgicalgenerator and local injection solution, and the invention ofendo knives have played a great role. Endo knives (Fig.1)

Flex knife (Olympus Optical Co, Ltd)2,3 is a dull andround tipped knife with a stopper at the tip of the sheath,and the sheath is flexible to absorb rapid change of thedepth of the knife. The length is also shortened optionally,it is suitable for the colorectum with thin wall. On thecontrary, it is difficult to dissect the submucosal layerwith severe fibrosis, and it is often stressful to regulate thelength of the knife.

Flush knife (Fujinon Optical Co, LTD)4,5,6 is a charac-teristic knife with a needle of 0.5 mm in diameter and 5projecting parts of 1, 1.5, 2, 2.5 and 3 mm in length. Forthe colorectal ESD, the 1.5 mm (or 2 mm) type is suitablefor the mucosal incision, and the length of 1.5 mm (or 1mm) type is for the submucosal dissection. The knife isset up to the projection length only by pushing out theneedle handle, which is maintained during the procedure.Using the tip of the sheath as a guard, the knife enablessafe and easy handling. Protecting the lesion and the mus-cle layer with the tip part of the sheath, the submucosallayer can be divided, and the severe fibrosis can be dissec-ted easily. Emitting a jet of water from the tip of a sheathenables lavage of the viewing field, and submucosal localinjection without replacement of operative instruments,which led to very efficient treatment. Flush knife was in-troduced after March 2003, and now it is used for the allcolorectal ESD, and good results are provided.

Hook knife (Olympus Optical Co, Ltd)7,8 is a device inwhich the tip of a Needle knife is bent at an angle of 90degrees to be hook shaped. The tip can be rotated and fi-xed in arbitrary directions. The handling is complicatedbut the knife is very safe because it can hook the object tosafer direction.

Insulation-tipped (IT) knife (Olympus Optical Co,Ltd)9,10 is a needle knife with the ceramic ball at the tip ofthe knife for the prevention of perforation. We cannot dis-sect with the tip, so a handling to force for a blade is nece-ssary. However, the handling should be parallel to the mu-scle layer to prevent the perforation and the damage of thelesion, so there is little usable situation of IT-knife in thecolorectum, especially colon, with many folds and flex-ions. Moreover, because of thin wall, the IT knife willoften roll up the muscle layer and the perforation easilyoccurs in the colorectum. The use of the IT knife in col-orectum is undesirable. B-knife (Zeon Medical Inc) is aneedle knife of the bipolar structure. Theoretically, thereis little heat damage to the deep part of the tissues. B-knife is thought to be safe for the organs with thin wall.

Triangle-tipped (TT) knife

(Olympus Optical Co, Ltd)

is a knife with the triangular tip. It can hook the objectwithout rotation. On the other hand, we have to separateall three corners from the muscle layer and the lesions.Therefore, the use of TT knife is limited to the situationthat enough submucosal elevation is kept.

ELECTRO SURGICAL GENERATOR (ESU)

Degree and the depth of the coagulation (the quality ofthe incision) to occur on the edge of incision are in pro-portion to the voltage and the strength of the electric dis-charge. The voltage changes according to the change ofthe impedance in the conventional generator which keepsa fixed output, so the quality of a uniform incision was

Development of Endo-knifes

Needle knife

IT knife

Hook knife

BB--knifeknife

Flush knife

Flex knife

Fig. 1

FIGURE 1DEVELOPMENT OF ENDO-KNIVES BASED ON THECONVENTIONAL NEEDLE KNIFE, SEVERAL ENDO-KNIVES FOR ESD HAVE BEEN DEVELOPED.

FIGURE 2HUGE RECTAL TUMOR.

18 T. Toyonaga et al. ACI Vol. LV

not provided. In ESU such as ICC or VIO (ERBE Elek-tromedizin GmbH) used for ESD, the voltage is automat-ically controlled to become always constant during the in-cision, so uniform and reproducible quality of incision canbe obtained. Furthermore, these ESU carrying Endo-Cutmode and various coagulation mode support the suitablecondition of ESD.

ATTACHMENT AND TRANSPARENT HOOD

An attachment is used to keep the clear visual fieldwhen getting into the flexion and the submucosal layer. Itis indispensable for the esophageal and colorectal ESD.

Small-caliber tip transparent (ST) hood (Fujinon OpticalCo, LTD) is a hood that the tip is narrow in the conicalshape, and it can secure the field of vision in the slightcrack. Because, the visual field is small and the hood iseasy to be smudged, it is not general-purpose.

HEMOSTATIC FORCEPS

Effective hemostasis and the prevention of bleeding arealso indispensable to safe procedure. Hot biopsy forcepswas misappropriated at first, but exclusive hemostaic for-ceps (Coagulasper Olympus Co, LTD) is already mar-keted. Current conduction after the grasping and retractingthe vessel is of importance to prevent the delayed perfora-tion.

METHODS OF ESD

MARKING

We place markings around the lesion to clarify the con-fine of the lesion in stomach and esophagus. However, theborder of the colorectal lesion is clear, there was no needto place marking in the colon and the rectum. (fig. 2)

LOCAL INJECTION

The solution is injected into the submucosal layer, tocreate the protrusion to the luminal side. Diluted sodiumhyaluronate is chosen for the colorectum which has thinwall in order to maintain the protrusion during the proce-dure.

MUCOSAL INCISION

The circumferential incision around the lesion is per-formed using endo knives.

SUBMUCOSAL DISSECTION

After the additional local injection, the submucosallayer is dissected.

COLLECTION AND THE HISTOPATHOLOGICAL DI-AGNOSIS

The removed lesion is collected and carefully examinedhistopathologically.

The arts of procedure in colorectal ESD (Fig.3)4,5,6,11,12,13,14,15

First, the mucosal incision from the anal side is to beperformed, then, the submucosal dissection has to be per-formed until the attachment could get into the submucosallayer . This procedure is particularly important for the le-sions which extend over the folds, and also the lesionswhich are at the location where the muscle layer rises per-pendicularly.

By incision and trimming to the anal (proximal) side ofthe lesion without performing the mucosal incision of theoral (distal) side, the lesion is pulled into the oral side andthe crack to approach the submucosal layer is easily pro-duced. On the contrary, when we first incise and trim theoral (distal) side of the lesion, the tension of mucosa onthe oral side disappears and the lesion does shift to theanal side.

Once we have got into the submucosal layer, we appro-priately add the mucosal incision from the lateral side tothe oral side, and proceed with the dissection.

FIGURE 2 E: RESECTED SPECIMEN. THE DIAMETER OF TUMOR155X140 MM,

FIGURE 2 F: VIEW OF 3 MONTHS AFTER ESD.

Br. 3 The results and limitations of endoscopic submucosal 19dissection for colorectal tumors

When the dissection is proceeded, the lesion hangsdown and gets possible to dissect extremely efficiently.We also change the posture of the patient appropriately,and use the gravity effectively. As for the important thing,when two-third of the dissection is performed, we mustcomplete the mucosal incision and trimming before the le-sion completely turns over into the oral (distal) side andcovers the object. We go ahead with the dissection fromthe anal (proximal) side again after the completion of thisprocedure. The final dissection is sometimes accompaniedwith difficulty. However, if the trimming of the oral sideis done to enough depth, the submucosal layer extends bythe weight of the lesion, and we should see the incisionborder of the distal (oral) side. Excision is completedsurely when we perform the last part of the dissection totrace this incision border.

LIMITATION AND "MUSCLE RETRACTING SIGN"

There is a limitation for the diagnosis of the invasion ofthe colorectal tumor, especially the lesion with protrusionlarger than 3 cm, even if we make full use of barium en-ema, endoscopic ultrasonograpy, and magnifying en-doscope. Sometimes we cannot remove the lesions whichseem to be resectable because of the deep wall invasion,on the other hand, we can often remove the lesions easilyeven with huge protrusion.

In the case of the massively invasive submucosal canceror invasive cancer, muscle layer might be retracted to thelesion at the invaded portion. when the retracted muscle isrecognized, the procedure should be discontinued becausethe continuation of the procedure raises the risk of perfo-ration and it means the lesion could be out of the indica-tions. We call this phenomenon "muscle retracting sign".When we perform ESD for the lesions with the large ses-sile protrusion, we prepare for the surgical operation.When we recognize "muscle retracting sign", we cope byperforming the radical surgical resection as soon as possi-ble, so that the lesion does not become necrotic.

RESULTS

The overall en-block complete resection rate was 95.2%(355/373). When we omit 12 cases that muscle retractingsign had been seen and procedure was discontinued, therate of en-block complete resection was 98.3% The medi-an tumor size was 30 mm (range: 6-158), and the medianspecimen size was 40 mm (range: 16- 165), and the medi-an procedure time was 58 min. (range: 15- 335). As forthe complication, the postoperative bleeding occurred in0.8 % (3 cases: no blood transfusion is needed). The intra-operative perforation occurred in 1.9 % (6 cases: 5 caseswere treated conservatively, 1 case was treated surgically)and the postoperative perforation occurred in 1 case(0.3%) treated surgically. Furthermore, after the inductionof the Flush knife, the tackling to the lesion with fibrosisbecomes easy. The frequency of combination use of devi-ces was decreased and the procedure time was shortenedparticularly in the difficult cases.

DISCUSSION

Even if endoscopic treatment can remove such large le-sions, it is only local resection. The suitable lesions are li-mited to those without metastasis, and in the colorectum,the lesions are as mentioned above. In the stomach, theselesions are concretely as below, 1) Intramucosal cancers,differentiated type, no lymphovascular invasion, and noulceration, irrespective of tumor size, 2) Intramucosalcancers, differentiated type, no lymphovascular invasion,and tumor less than 3cm in size, irrespective of ulcerationfindings, 3) Minimally invasive submucosal cancers (in-vasion depth 500 m), differentiated type, no lymphovas-cular invasion, and tumor less than 3cm in size. In theesophagus, these lesions are intramucosal cancers (inva-sion depth m1-m2), 2/3 around the lumen16,17.There is li-mitation for the preoperative diagnosis too, so we mustjudge whether curative resection has been done by thecorrect histopathological diagnosis of the specimen. Espe-cially, the judgment such as the depth of submucosal in-vasion and lymphovascular invasion is crucial. The con-ventional EMR forced many lesions to be removed by thepiecemeal resection. The piecemeal resection has theproblems that many recurrences often occur by the mis-judgment of the margin, and correct histopathological di-agnosis is difficult by the damage of speciemen. Themeaning that ESD has enabled en-block resection is ex-tremely great. The problems of ESD will be the high tech-nical difficulty and long procedure time, and high fre-quency of the complication. In the colorectum, the mu-cosa is easy to cut, and a little bleeding occurs, there is notso much difficulty to perform smooth dissection if thegood field of vision is provided.

FIGURE 3 A,B,C,DLST-NG LOCATED IN THE TRANSVERSE COLON


The tumor size and location do not influence the degreeof difficulty, and only make the difference of the proce-dure time. The difficult cases of colorectal ESD are the le-sions with severe fibrosis. The most of those are nongranular type of lateral spreading tumor (LST-NGs). Alsothe submucosal layer of LST-NGs is thin, and the lesionsoften extend over the folds and the flexion. Therefore,LST-NGs are the lesions which are the most difficult for

ESD. In case of the severe fibrosis, it is not easy to keepthe clear field of vision with the normal attachment. In ad-dition, it is difficult to dissect the severe fibrosis withFlexknife because its tip is dull and sheath is soft. How-ever it is not so difficult with Flush knife. With Flushknife, operators can protect the muscle layer and the le-sion and go into the submucosal layer with the tip of thesheath.

The major complication of ESD consists of the perfora-tion and bleeding, and it is distributed for the intraopera-tive and postoperative. Although the frequency dependson the operator and institution, it is generally regarded asaround 3-10%.

Above all, the perforation is the most serious complica-tion, and the recognition is widely spreads out that the fre-quency of the perforation is extremely higher in colorectalESD than in the gastric ESD. However, the frequency isactually high when IT knife is used, but it is not so highwhen operators use the devices which dissect with the tip,such as Flush knife. Furthermore, the intraoperative perfo-ration by ESD is pinhole shaped, and conservative treat-ment is possible to close the hole by the clip. If the trans-mural burn happens even if there is no intoraoperativeperforation, the necrotic region may fall off to cause thedelayed perforation. This is the same phenomenon thathas been reported as post polypectomy coagulation syn-drome caused by the resection with the snare and hot bi-opsy forceps. We experienced the delayed perforation inone case that the operator coagulated too much the bloodvessels on the bottom of the ulcer. Histopathologically, inthe resected specimen, the muscle layer was partly miss-ing, and the remained muscle layer fell into the necrosiswidely by the coagulation. After the measures to conductthe current after grasp and traction with small hemostaticforceps, there is no delayed perforation. The postoperativebleeding is experienced in the case of the lesion on theileocecal valve, rectum, and anal canal and recognizedwith the bloody diarrhea. We have no clinically trouble-some case, and there was no patient who needed the bloodtransfusion. There were only two cases that needed coagu-lation with hemostatic forceps.

ESD needs not only the technique of the operator, butalso the cooperation with the assistant. It is necessary forthe assistant to understand the whole procedures of ESD,and also, the characteristic and the use of devises. For theinduction of ESD, the conference, study group, and livedemonstration should be used to collect knowledge. Thesmooth introduction and the training system of ESD arethe important themes in the future.

CONCLUSION

By the development of ESD, endoscopic treatment hasmet a new era. Such lesions that are diagnosed to have nolymph node metastasis can be removed completely by thismethod, which is expected to greatly contribute to theQOL of the patients. Even in the colorectum, ESD can beperformed safely by the proper choice of the devices andappropriate resection strategy. However, there is a limita-tion for the preoperative diagnosis of the lesions with

FIGURE 3 E,F,GVIEW AFTER ESE, RESECTED SPECIMEN AND HIS-TOLOGIC CROSS SECTION

FIGURE 4 A, B,C, DMUSCLE RETRACTING SIGN


"muscle retracting sign" which is the index of the discon-tinuation of ESD.

SUMMARY

REZULTATI I OGRANI^ENJA ENDOSKOPSKE SUB-MUKOZNE DISEKCIJE KOLOREKTALNIH TUMORA

Kolorektalni tumori koji se mogu le~iti endoskopski sutumori bez metastaza u limfnim ~vorovima, kao {to suadenomi, intramukozni karcinomi i minimalno invazivnisubmukozni karcinomi (dubina invazije manja od 1000m,dobro i srednje diferentovani, bez limfovaskularne invaz-ije). Nova endoskopska tehnika, endoskopska submuk-ozna disekcija (ESD) omogu}ava "en-bloc" resekciju tu-mora bez obzira na njegovu veli~inu i lokalizaciju. U ciljulak{eg, sigurnijeg i efikasnijeg izvodjenja ESD-a izumelismo "water jet" endoskopske no‘eve kratkog vrha ("Flushno"). Ovaj no‘ izbacuje mlaz vode sa svog vrha i timeomogu}ava disekciju submukoznog sloja bez potrebezamene instrumenata a to vodi efikasnijem tretmanu."Flush no" je posebno efikasan u uklanjanju tumora don-jeg rektuma i analnog kanala, regija sa mnogo krvnihsudova. Endoskopskom submukoznom disekcijom le~ilismo 361 kolorektalni tumor u periodu od juna 2002. dojula 2007. godine sa stopom kompletne, "en-bloc" resek-cije tumora od 98,3%. Znak "povla~enja mi{i}a" je vidjenu 12 slu~ajeva. Ovaj znak ukazuje na potrebu odustajanjaod dalje endoskopske submukozne disekcije, ali ga jenemogu}e otkriti preoperativno. Postoperativno krvarenjese javilo u 0,8% slu~aja (3 puta: bez potrebe za transfuzi-jom). Intraoperativna perforacija se desila u 1,9% (6slu~ajeva: 5 puta le~eno konzervativno, a jednomhirur{ki) a kod slu~aja postoperativne perforacije (0,3%)le~enje je zavr{eno hirur{ki. Endoskopska submukoznadisekcija je izuzetno efikasan na~in le~enja kolorektalnihtumora, i uz pravilan odabir instrumenata i strategije,mo‘e se izvesti bezbedno.

Klju~ne re~i: endoskopska submukozna disekcija(ESD); Flush no; kolorektalni tumori;znak povla~enja mi{i}a

REFERENCES

1. Japanese Society for the cancer of colon and rectum.Treatment guidelines for colorectal cancer ( in Japanese).Tokyo: Kanehara; 2005.

2. Yahagi N, Fujishiro M, Kakushima N, Kobayashi K,Hashimoto T, Oka M, et al. Endoscopic submucosal dis-section for early gastric cancer using the tip of an electro-surgical snare (thin type). Digestive Endoscopy 2004; 16:34-48.

3. Kodajima S, Fujishiro M, Yahagi N, Kakushima N,Ichinose M, Omata M. Endoscopic submucosal dissectionfor gastric neoplasia : experience with the flex-knife. ActaGastroenterol. Belg 2006; 69: 224-9.

4. Toyonaga T, Nishino E, Hirooka T. Invention ofwater jet short needle knives (Flush knife) for endoscopicsubmucosal dissection. Endoscopia Digestiva 2005; 17:2167-74. (in Japanese with English abstract)

5. Toyonaga T, Nishino E, Hirooka T et al. Invention ofwater jet short needle knives for endoscopic submucosaldissection. Endoscopy 2005; 37: A19

6. Toyonaga T, Nishino E, Hirooka T et al. Use of shortneedle knife for esophageal endoscopic submucosal dis-section. Digestive Endoscopy. 2005; 17: 246-252

7. Oyama T, Tomori A, Hotta K, Morita S, Kominato K,Tanaka M, Miyata Y. Endoscopic submucosal dissectionof early esophageal cancer. Clin Gastroenterol Hepatol2005; 3: S67-70

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Legend to figuresFig.1 Development of Endo-knives based on the conventional needle knife, several endo-knives for ESD have been developed. Fig.2 Huge rectal tumor. A: It is a huge tumor which is accompanied with the high protrusion extending almost entire rectum. The ranges of the

tumor exceed over 5/6 circumferential.B: Mucosal incision using a Flush knife. C: When the dissection is proceeded, the lesion hangs down andgets possible to dissect extremely efficiently. We also change the posture of the patient appropriately, and use the gravity effectively D: View just af-ter ESD.

Fig.2 E: Resected specimen. The diameter of tumor was 155x140 mm, and that of specimen was 165x150 mm. histopathological evaluationshowed that it was pM, tub1 in adenoma, ly0, v0, HM0, VM0.

Fig.2 F: View of 3 months after ESD.The ulcer after ESD was well healed to be a scar. The deformation of rectum was detected, but the insertionof the scope was easy, and there was no symptom of stricture.

Fig.3 LST-NG located in the transverse colon. A: LST-NG lesion extending over a fold. A biopsy scar by a referring endoscopist was recognizedin the oral side of the center of the lesion, and a slight concentration of the fold was also detected. The obvious Vn pit pattern was not found. B, C:Mucosal incision from the anal side was performed, then, the submucosal dissection was performed until the attachment could get into the submu-cosal layer. Without performing the mucosal incision of the oral (distal) side, the lesion was pulled into the oral side and the crack to approach thesubmucosal layer was easily produced. D: Dissection of the fibrosis by the Flush knife. There was severe fibrosis under the biopsy scar. Even in thiscase, Flush knife enabled the precise dissection by using tip part of the sheath as a guard and a protector to the muscular layer and the lesion.E:View just after ESD The dissected side was observed homogeneously. F, G: Resected specimen and histologic cross section. 0-IIa (LST-NG), the di-ameter of tumor 30X20mm, tub1, pSM1(500 m), ly0, v0, pHM0, pVM0, EA The long diameter of the lesion was 30mm and the submusocal inva-sion was detected in 2 parts (#12). The edge of resection was free from tumor, and there was no lymphovascular invasion. The severe fibrosis wasrecognized in the submucosal layer under the biopsy scar (#11). LST-NGs are indicated to have high frequency of submucosal invasion and diffi-culty in diagnosing the extent of invasion with the detailed observation of pit pattern. Such lesions are the best adaptation of ESD.

Fig.4 Muscle retracting sign. A: LST-G located at the sigmoid colon: Large-size nodes were detected to step over the fold. There was no definiteobservation to suggest the massive invasion. B, C: At first, the procedure was smooth but the muscle layer was recognized to be retracted into the tu-mor in the shape of a tent. D: ESD was discontinued, and surgical resection was performed. Histopathological evaluation revealed massive tumor in-vasion to the subumucosal layer (SM2) with the thick muscle layer retracted into the tumor.


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dissection for colorectal tumors - doiserbia · the oral side, and proceed with the dissection....

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