colorectal cancer is one of the most commonly diagnosed malignancies in western countries and represents a major cause of morbidity and mortality associated with cancer 1 .
detection and endoscopic resection of early stage colorectal tumors as well as precursor lesions is a well established approach to prevention and treatment of colorectal cancer .
endoscopic mucosal resection ( emr ) is usually used for endoscopic removal of flat and sessile lesions of the large bowel . for tumors measuring    20  mm
it is especially difficult to determine the lateral spread of the tumor to ensure complete removal .
piecemeal resection is associated with a higher rate of local tumor recurrence in comparison with en bloc emr 2 
 3 
 4 .
endoscopic submucosal dissection ( esd ) is a novel therapeutic procedure with the major advantage being its ability to achieve a high level of en bloc resection and low level of local recurrence for flat and sessile colorectal lesions regardless of size . on the other hand ,
colorectal esd is associated with significant technical difficulty , longer procedure time , and increased risk of complications , especially perforations , in comparison with emr 5 
 6 .
colorectal esd is considered to be a more difficult and  dangerous  procedure than gastric esd . in japan , it is necessary to gain experience in gastric esd before starting to practice esd in the colon , usually under the supervision of an expert 7 
 8 . in western countries
, it is very difficult to follow the same learning pattern because of the different epidemiological situation ( the incidence of gastric cancer is higher in japan and a lower percentage of cancers are diagnosed at an early stage in the west ) and the very limited number of practitioners with expertise in colorectal esd 8 .
several factors have been implicated in an increased risk of incomplete or complicated dissection 9 
 10 .
it is important to establish a better approach to the difficulties of implementing colorectal esd during the learning period in western settings , as well as the factors associated with the risk of complications .
we report our experience with esd for sessile and flat rectal and sigmoid colon lesions in a high - volume center in russia .
during the period from november 2009 to september 2013 , 44 patients with sessile and flat rectal and sigmoid colon lesions underwent esd at the department of endoscopy , vladivostok clinical railway hospital ( russia ) .
the clinical indications for esd included sessile and flat rectal and sigmoid colon lesions with one of the following features : ( 1 ) tumor size   20 mm ; ( 2 ) tumor recurrence after previous emr .
all of the relevant data have been taken from the standard esd protocol adopted by the department .
lesion size has been estimated by comparison with the span of open ( 7  mm ) biopsy forceps ( fb-24u-1 ; olympus , japan ) .
the colonic preparation was achieved by administration of a split - dose ( 2 and 2 liters ) of macrogol 4000 solution ( beaufour ipsen international , france ) before the procedure .
all of the patients underwent conscious sedation using the intravenous administration of propofol and analgesia with fentanyl .
one endoscopist with experience in endoscopic mucosal resection in the large bowel ( more than 200 cases ) performed all procedures .
procedure time , tumor size and location , gross morphology , the presence of fibrosis , and morphological findings were analyzed .
the main outcomes were en bloc and r0 resection rate , and number of perforations .
for an analysis of the learning curve , the whole study time was divided into two periods : first period : resections 1    22 ,
the degree of submucosal fibrosis was classified into three types : f0 , no fibrosis ; f1 ; mild fibrosis ; f2 , severe fibrosis 10 .
total procedure time was defined as the time between the beginning of the submucosal injection and the completion of the dissection .
complications were classified as immediate ( during the procedure ) or delayed ( after completion of the procedure ) .
perforation was defined as a hole in the muscle layer detectable endoscopically with free air outside the colonic lumen demonstrated on image studies .
bleeding was considered clinically relevant in the case of a hemoglobin drop   1  g / dl .
the esd procedure was classified as technically difficult in the case of procedure time >  120 minutes and/or piecemeal resection .
esd procedures were conducted with a gastroscope ( eg-530  d , fujifilm europe gmbh , germany ) with a disposable distal attachment ( d-201 , olympus , japan or dh-28gr , 29cr ; fujifilm medical co. , japan ) on the tip . 
a vio 200  d electrosurgical unit ( erbe elektromedizin , germany ) was used for electrical cutting and coagulation .
carbon dioxide insufflation with a gw-1 delivery system ( fujifilm europe gmbh , germany ) was used in all esd cases .
a 10  % glycerin solution was used for submucosal injections using a 21-gauge injection needle ( nm-400l-0421 , olympus , japan ) outside the tumor margin . a flush knife or flush knife - bt with a 2.0-mm - long tip ( fujifilm europe gmbh , germany ) connected to a waterjet pump
was used to perform all steps in the esd procedure : mucosal cut (  endo cut i  regime , effect 2 , duration 3 , interval 3 ) , submucosal dissection (  forced coag 
regime , effect 2 , 40  w ) , and small - vessel coagulation (  soft coagulation  regime , effect 7 , 100  w ) .
submucosal injection of 10  % glycerin solution ( via injection needle ) and waterjet injection of saline solution using the flush knife were repeated during the procedure to maintain sufficient submucosal elevation during the procedure . a hemostatic forceps ( coagrasper , fd-411ur , olympus )
was used to prevent or stop significant bleeding from large vessels and to coagulate visible vessels in the post - procedure ulcer base (  soft coagulation 
the specimen was stretched and pinned onto a hard plate before being sent to the pathology department .
histological evaluation was performed according to the standard principles for colorectal emr and esd specimens 11 .
the pathological diagnosis was based on the vienna classification of gastrointestinal epithelial neoplasia 12 . en
bloc resection was defined as when the lesion was resected as a whole piece , and r0 resection was when the resected specimen was revealed to be free of tumor in both vertical and lateral margins .
local recurrence was defined as a histopathologically confirmed neoplastic lesion found at the site of the esd scar .
all patients received detailed information about the procedure , alternative approaches , risks of complications and additional surgery , and provided written informed consent before participating in any protocol - specific procedures .
all data were analyzed using the chi - squared test and fisher s exact tests . for lesion size and procedure time ,
the pearson correlation coefficient was used to measure the strength of the association between two variables .
forty - four patients took part in the study ( 23 men , 21 women ) .
the mean age of the patients was 63.84    1.46 years ( range 41   
the mean size of the tumors was 34.77    3.26  mm ( range 10    120  mm ) .
all tumors were situated in the rectum or sigmoid colon . according to the paris classification
correlation between the serial number of the esd procedure and both the tumor size and procedure time was weak ( r  =  0.19 and 0.17 , respectively ) . 

table  1 shows the tumor characteristics , resection rates , and procedure time during the two study periods . in 37 cases ( 84.1  % ) ,
four tumors were removed in two fragments , and three tumors in three to four fragments .
the mean size of the lesions removed in piecemeal fashion was higher than that for tumors resected en bloc , 44.0    4.55  mm and 33.03    3.73  mm , respectively , but the difference was not statistically significant ( p  =  0.22 ) .
histological examination revealed low grade dysplasia , high grade dysplasia and cancer in 10 , 22 , and 12 cases , respectively .
lgd , low grade dysplasia ; hgd , high grade dysplasia . the mean procedure time was 119.95    11.22 minutes ( range 25    360 minutes ) .
there was a high direct positive correlation between tumor size and operation time ( r  =  0.83 , p  <  0.0001 , 0.95 and 0.99 confidence interval for rho 0.71    0.904 ) .
operation time was shorter in the en bloc resection group than in the piecemeal group , 108.75    12.03 minutes and 179.14    19.85 minutes , respectively ( p  =  0.019 ) .
the mean procedure time did not differ between the first and second 22 esd interventions : 101.85    11.74 minutes and 136.47    18.18 minutes , respectively ( p  =  0.12 ) .
severe , mild and absent submucosal fibrosis were diagnosed in 15.9  % , 15.9  % , and 68.2  % of cases , respectively .
tumor size was not a significant predictor of severe fibrosis , although the mean size of the lesions with f2 fibrosis was higher than that for tumors with f0    f1 fibrosis , 40.0    5.34  mm and 33.78    3.74  mm , respectively ( p  =  0.49 ) .
three out of seven f2 tumors were flat ( two lst - ng ( laterally spreading tumor , non - granular type ) and one iia ) and four were sessile ( is ) .
one lesion ( lst - ng ) was situated on the anastomotic site and in one case ( iia ) , there was a recurrence after unsuccessful emr .
severe submucosal fibrosis was diagnosed in four out of seven cases of piecemeal esd and in three cases of en bloc resection ( p  =  0.0074 ) .
the procedure in patients with f0    f1 fibrosis was shorter than in patients with f2 fibrosis , 111.75    12.22 minutes and 162.28    23.88 minutes , respectively , but the difference did not reach the level of statistical significance ( p  =  0.093 ) .
all cases of perforation were diagnosed during the procedure and were successfully treated with endoscopic clipping . a sigmoid colon perforation treated with endoclips is shown in fig .  1 . 

endoscopic submucosal dissection ( esd ) in the sigmoid colon . a laterally spreading tumor , non - granular , pseudo - depressed type ( lst - ng - pd ) in the sigmoid colon ; b marking around the tumor borders ; c dissection of the submucosa ( f2 fibrosis ) ; d visible perforation hole ; e perforation was closed with clips and endoloops ; f scar 4 months later .
three perforations occurred during the first half and two during the second half of the esd procedures .
there was no difference between procedures complicated by perforation and uneventful esd by tumor size ( 31.0    6.0  mm and 35.25    3.61  mm , respectively p  =  0.68 ) and resection time ( 104.0    23.48 minutes and 122.0    12.35 minutes , respectively p  =  0.62 ) .
at the same time , severe submucosal fibrosis was diagnosed in four out of five cases complicated by perforation and in three cases of uneventful esd ( p  =  0.0012 ) .
table  2 shows the comparison of tumor and procedure characteristics in patients with and without perforations associated with the esd procedure . in total
, 19 procedures ( 43.1  % ) were classified as technically difficult due to the following factors : procedure time >  120 minutes , 12 patients ; combination of procedure time >  120 minutes and piecemeal resection , six patients ; and piecemeal resection , one patient .
mean tumor size was significantly larger in the difficult esd group compared with the standard esd group , 48.31    5.96 and 24.48    1.75  mm , respectively ( p  =  0.0001 ) .
the majority of difficult esd procedures were performed for tumors of the sigmoid colon , but the difference did not reach a level of significance ( p  =  0.06 ) .
table  3 shows a comparison of the tumor characteristics in the standard and difficult esd groups .
no cases of clinically significant intraprocedural or postprocedural hemorrhage were noted . there were two cases of self - limited postprocedural hemorrhage , and no cases of surgery or death associated with complications of esd .
two patients had cancer with submucosal invasion >  1  mm and one had a blood vessel invasion .
endoscopic mucosal resection ( emr ) is a well - established method for treatment of colorectal epithelial neoplasms . in lesions larger than 20  mm and in cases of severe submucosal
fibrosis , emr often results in piecemeal resection associated with the difficulties of histopathological assessment of r0 resection , the risk of incomplete resection and local recurrence 2 
 3 
 4 .
endoscopic submucosal dissection ( esd ) is a relatively new technique that is now established in japan for en bloc resection of large benign and early malignant lesions 13 . while esd reduces local recurrence rates compared to emr , it is technically challenging , risky , and time consuming 5 
 6 
 14 .
compared with gastric lesions , esd in the colorectum is more difficult owing to anatomical features   
owing to its technical difficulty , complication risks , and relatively long learning curve , esd for colorectal lesions is rarely used in western countries and emr is currently the standard treatment .
a step - by - step approach to accumulating experience in colorectal esd is desirable for adopting this technique 7 
 8 . before first attempting esd in the large bowel ,
experience with at least 30 gastric esd cases has been recommended in japan 16 
 17 . in the west ,
opportunities to follow a japanese esd training algorithm are limited by the low rates of early gastric cancer 8 
 18 . at the same time , a number of authors have reported a relatively rapid learning curve and low complication rats for colorectal esd 19 
 20 
 21 .
several factors , including tumor location and size as well as severe submucosal fibrosis have been implicated in an increased risk for incomplete or complicated dissection 9 
 10 .
the incidence and implications of these factors during the learning curve have as yet not been well established . in this single - center study ,
the results of 44 esd procedures for rectal and sigmoid colon lesions have been described .
all interventions have been performed by a single specialist with experience in endoscopic mucosal resection in the large bowel and with limited experience ( 19 cases ) of gastric esd .
the en bloc and r0 resection rates were the same    84.1  % .
these figures are lower than reported by authors from high volume asian centers 14 
 22 
 23 , but comparable to en bloc and r0 resection rates according to european data 19 
 21 
 24 .
procedure time in the study ( 120 minutes ) was much longer than reported by japanese authors 14 
 22 
 23 .
however , the current results are comparable to western data presented by probst et al .
larger tumor size and piecemeal resection were associated with longer procedure times in the current series .
tumor size is regarded as one of the factors predicting the procedural time of esd , at least for gastric lesions 25 
 26 .
inability to perform en bloc esd usually reflects a difficult procedure that , in turn , leads to increased time required for the intervention 9 . in this study ,
at the same time , larger tumor size was the single significant risk factor for technically difficult esd .
almost two - thirds of difficult esds were performed for lesions of the sigmoid colon .
10 reported that , in cases of lesions with severe ( f2 ) fibrosis , the rate of complete en bloc resection was low , and did not improve significantly even with growing operator experience .
several studies have demonstrated that the presence of fibrosis is an independent risk factor for perforation during colorectal esd 10 
 27 . at the same time , tumor size and location are conceded by several authors to be factors associated with difficult esd and increased risk of perforation 9 
 28 .
several factors have been implicated as a cause of severe submucosal fibrosis : previous emr attempts , multiple biopsies and inflammatory bowel disease .
there are also reports that the macroscopic characteristics of the lesions can be used to predict the risk of fibrosis , but the results are still controversial .
different authors have suggested that the incidence of f2 fibrosis was higher in lst - g ( laterally spreading tumor , granular type ) 10 or lst - ng and large is tumors 9 . in our series ,
f2 fibrosis was reliably predicted by patient s history ( previous unsuccessful emr ) and characteristics of the lesion ( tumor on the anastomosis site ) in two cases . in another five cases of severe fibrosis ,
large ( >  40  mm in diameter ) sessile lesions ( four tumors ) prevailed .
a relatively long period of growth in combination with chronic traumatization due to peristaltic movements can explain the high risk of fibrosis in such lesions .
the possible role of endoscopic biopsy has not been analyzed owing to lack of relevant data .
the number of perforations ( 11.4  % ) in our study was high in comparison to most of the published data ( 1.8    7.4  % ) 14 
 21 
 22 .
to the best of our knowledge , the highest level of perforations during colorectal esd ( 20.4  % ) was reported by kim et al .
the level of perforations would have been regarded as unacceptable if surgery had been required for correction .
fortunately , most perforations can be managed successfully with nonsurgical treatment 14 
 22 
 23 
 27 .
we failed to show any difference in procedure time , en bloc resection rate as well as in the number of perforations between the first and second 22 interventions .
probst et al . reported that a clear learning curve was apparent over time , with resection rates increasing and procedure times decreasing significantly after the first 25 esd procedures in the rectosigmoid 19 .
, the operating time per square centimeter significantly decreased after 20 esd procedures 20 . at the same time , based on their analysis of 120 colorectal esds , hotta et al . concluded that approximately 40 procedures were sufficient to acquire skill in avoiding perforations during the esd procedure , and
approximately 80 procedures must be carried out to acquire skill with esd for large colorectal tumors 28 .
according to sakamoto et al . , trainee endoscopists with experience in gastric esd can perform it safely and independently in the colon after preparatory training and experience with    30 cases . at the same time
, the authors mentioned that the procedure time and en bloc resection rate were not significantly different among the training periods 29 .
saito et al . reported that the risk of perforation was related to the number of esd procedures performed , that is , the risk is higher when the endoscopist had performed less than 100 procedures 30
. the main limitations of this study include the fact that it was a single center study and limited to lesions of the distal colon .
we can conclude that esd in the distal colon is feasible , effective , and a relatively safe procedure for western endoscopists . despite the substantial rate of perforations ,
severe submucosal fibrosis was an important factor associated with a low rate of en bloc resection and a high risk of perforation during the learning curve for colorectal esd
. it might be reasonable to start with smaller lesions and avoid cases with predictable f2 fibrosis during the training period .
colorectal esd is associated with a relatively long learning curve , and 22 esd cases might not be sufficient to improve en bloc resection rates , reduce procedure times and the number of perforations during a further 22 resections .
prospective randomized trials comparing emr and esd are awaited in europe to demonstrate the long - term results , the benefit of esd over piecemeal emr and also to determine the indications for esd vs. emr in different clinical settings .
 
 background and study aims : colorectal endoscopic submucosal dissection ( esd ) is associated with significant technical difficulty , long procedure time , and increased risk of complications , especially perforation . 
 this study aimed to determine the factors associated with clinical results of esd during the learning curve . 
 
 patients and methods : in total , 44 patients with sessile and flat rectal and sigmoid colon lesions underwent esd from november 2009 to september 2013 .  
 the procedure time , resection method , tumor size , location , gross morphology , presence of fibrosis , histologic findings , rates of en bloc and piecemeal resections and perforation were analyzed . 
 the esd procedure was classified as technically difficult in the case of procedure time >  120 minutes and/or piecemeal resection . 
 the whole study time was divided into two periods : first period : resections 1    22 , second period : resections 23    44 . 
 
 results : en bloc and r0 resection have been achieved in 84.1  % of lesions . 
 the mean procedure time was 119.95    11.22 minutes ( range 25    360 minutes ) . 
 perforation was seen in five cases ( 11.4  % ) . 
 a larger tumor size was a risk factor for difficult esd ( p  =  0.0001 ) . 
 a finding of fibrosis was a risk factor for piecemeal esd ( p  =  0.0074 ) , and perforation ( p  =  0.0012 ) . 
 there was a high direct positive correlation between tumor size and operation time ( r  =  0.83 , p  <  0.0001 , 0.95 and 0.99 confidence interval for rho 0.71    0.904 ) . 
 there was no significant difference between the first and second period in terms of mean procedure time , en bloc resection or complication rate . 
 
 conclusion : a larger tumor size was associated with technically difficult esd . 
 severe submucosal fibrosis was a risk factor for both piecemeal resection and perforation . 