LEARNING CURVE FOR ENDOSCOPIC SUBMUCOSAL DISSECTION OF LARGE COLORECTAL TUMORS

Background and Aim: No studies have previously described the learning curve for colonic endoscopic submucosal dissection (ESD). The aim of the present study was to describe the learning curve for ESD of large colorectal tumors based on a single colonoscopist's experience. Methods: ESD was carried out for 120 colorectal tumors in 115 patients (68 males, median age 70 years). All procedures were carried out by a single experienced colonoscopist. The cases were grouped chronologically into three periods: (1st): cases 1–40; (2nd): cases 41–80; and (3rd): cases 81–120. Results: The learning curve was the changes in proficiency over time. Proficiency was expressed as procedure time per unit area of specimen. In the 1st, 2nd and 3rd periods, the proficiencies were 18.9, 12.6 and 12.9 (min/cm²), respectively. The proficiencies in the 2nd and 3rd periods were significantly shorter than in the 1st period (t‐test, P < 0.05). The en‐bloc resection rates of the 1st, 2nd and 3rd periods were 92.5% (37/40), 90% (36/40) and 97.5% (39/40), respectively. The en‐bloc and R0 resection rates of the 1st, 2nd and 3rd periods were 85% (34/40), 77.5% (31/40) and 92.5% (37/40), respectively. The perforation rates of the 1st, 2nd and 3rd periods were 12.5% (5/40), 5% (2/40) and 5% (2/40), respectively. Conclusion: Based on our analysis of the learning curve, approximately 80 procedures must be carried out to acquire skill with ESD for large colorectal tumors. However, approximately 40 procedures were sufficient to acquire skill in avoiding perforations during the ESD procedure.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL NEOPLASIA

Aim: Endoscopic submucosal dissection (ESD) has been positively applied to and gradually standardized for early gastric cancer; however, it is not widely used in the colorectum because of its technical difficulty. Methods: To increase the safety and ease of carrying out colon ESD, we developed a new scissors‐type device that we call the stag beetle knife (SBK). Here we report on our efforts to assess the efficacy and safety of colon ESD using the SBK. Results: ESD was carried out using SBK in 25 patients with colorectal neoplasia. All lesions were treated safety and easily, without any unexpected incisions. No delayed hemorrhage and perforation occurred. An en‐bloc resection and a negative resection margin were obtained in all cases. Conclusion: ESD using the SBK can be carried out with greater ease and safety for colorectal neoplasia.     

TECHNIQUES AND PITFALLS OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL TUMORS

Endoscopic submucosal dissection (ESD) for colorectal tumors is steadily being developed. Safety and standardization of ESD for colorectal tumors have not been yet established because of the technical difficulties and the unsuitable anatomical characteristics of the colon and rectum. The authors mainly use a Flex knife for mucosal incision and a Hook knife for submucosal dissection to perform ESD safely. Skillful colonoscopic control, selection of scope, distal attachment tip hood, adequate high‐frequency generator and correct approach strategy should all be considered for safe performance of ESD. However, the incidence of indicative lesions is rare because the majority of colorectal tumors are adenomatous large laterally spreading tumors, which can be cured by intentional endoscopic piecemeal resection. At present, ESD for colorectal tumors should be performed only at central facilities that have expert colonoscopists. With the development of new devices and associated techniques, technical standardization of ESD for colorectal tumors is expected in the near future.     

ENDOSCOPIC SUBMUCOSAL DISSECTION WITH SHEATH‐ASSISTED COUNTER TRACTION FOR EARLY GASTRIC CANCERS

Aim: Endoscopic submucosal dissection (ESD) is associated with frequent complications, such as bleeding and perforation. The procedure is technically difficult, requires considerable skill and is longer than conventional endoscopic mucosal resection (EMR). Thus, non‐invasive tools and methods are needed to facilitate direct visualization of the submucosal layer during ESD. Methods: An insulation‐tipped (IT) knife was inserted into one channel, and a conventional injection sheath was inserted to the other channel of a double‐channel fiberscope. The submucosal layer was lifted via a circumferential incision using the conventional injection sheath for visualizing cutting lines, and the submucosal layer under the lesion was directly dissected from the underlying muscularis propria. Results: Sheath‐assisted traction resulted in successful ESD with en bloc resection in all 25 patients. Hemostasis and manipulation of blood vessels were uncomplicated and dissection was completed safely, without either bleeding or perforation. The movement of the sheath was not suppressed while lifting the submucosal layer and the IT knife could be moved freely, which allowed submucosal dissection independently of the sheath movement. Conclusion: Sheath‐assisted traction ESD, using simple materials and methods, has several advantages over other standard traction methods. Our procedure is straightforward, safe, non‐invasive, cost‐effective and uses readily available instruments to enhance visualization of cutting lines.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR RECURRENT GASTRIC TUMORS

Endoscopic resection has been accepted as the standard treatment for intramucosal gastric tumors of differentiated type. However, the indication was limited to small tumors to achieve en bloc resection and prevent local recurrence in cases of conventional endoscopic mucosal resection (EMR) such as the strip biopsy and the cap technique. To avoid multi‐fragmental resection, we have developed endoscopic submucosal dissection (ESD) as a new endoscopic resection technique. ESD is a remarkable technique, because we make it possible to remove the lesions en bloc regardless of size, shape, coexisting ulcer, and location. However, it is difficult or impossible to resect recurrent tumors en bloc in conventional EMR owing to hard fibrosis, and some patients need laparotomy. Using ESD, we can dissect the submucosal layer as we directly look at the submucosa, and remove the lesion safely and reliably even in cases of hard fibrosis. The key to treatment of recurrent tumors in ESD are as follows: (i) using enough submucosal injection solution (we use a mixture of Glyceol and 1% 1900 kDa hyaluronic acid preparation); (ii) incising the mucosa without fibrosis; (iii) understanding characteristics of various cutting devices, and changing other devices in difficult situations. In these ways we can remove the majority of the recurrent tumors en bloc. Hence, we consider that ESD is a very effective treatment which achieves excellent en bloc and complete resection rates and enables patients with intramucosal gastric tumors to a recurrent‐free survival even in recurrent tumors.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.     

ENDOSCOPIC SUBMUCOSAL DISSECTION OF COLORECTAL LESION

Endoscopic submucosal dissection (ESD) has been developed for en‐bloc resection of mucosal lesions of the gastrointestinal tract. It enables us to resect almost all mucosal and slightly submucosal invasive tumors, regardless of size and shape, even in the colon. Therefore, preoperative diagnosis, especially for the depth of invasion, is very important to determine the treatment strategy. The shape of the lesion, its pit pattern and also EUS findings are very useful in estimating the depth of invasion. We use an EndoEcho system with ultrasonic probe, which gives us both radial and linear image of the lesions. Remodeled three‐dimensional (3D) images are also very useful in evaluating the size and the expansion of the lesion when it is located on a fold. Although the large intestine involves structural and technical difficulties, we conduct en‐bloc resection by ESD while exercising various ingeunities in preparation, endoscopes, use of instruments and local injections. ESD is the reliable technique, which allows en‐bloc resection of gastrointestinal mucosal lesions, and has a excellent chance of success in the treatment of early stage colorectal cancer.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR THE RELIABLE EN BLOC RESECTION OF COLORECTAL MUCOSAL TUMORS

Scheduled piecemeal resection has been actively conducted for granular type laterally spreading tumor (LST‐G) in Japan, as long as a definite preoperative diagnosis is made. However, en bloc resection is desirable for depressed lesions (e.g. IIc lesion) as well as non‐granular type laterally spreading tumor (LST‐NG) since they have considerable high risk for submucoasl invasion and require precise histopathological evaluation. Endoscopic submucosal dissection (ESD) has been developed for the en bloc resection of mucosal tumors of gastrointestinal tract and widely applied especially in gastric lesions. Although the large intestine involves structural and technical difficulties, we conducted en bloc resection by ESD while exercising sorts of ingenuity for preparation; endoscopes, instruments, local injections, and others. ESD is a reliable technique that allows en bloc resection of gastrointestinal mucosal lesions, and even has a splendid possibility for the treatment of early stage colorectal cancer.     

NOVEL TECHNIQUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN EXTERNAL GRASPING FORCEPS FOR SUPERFICIAL GASTRIC NEOPLASIA

Endoscopic submucosal dissection (ESD) for early stage gastric cancer (EGC) has improved the success rate of en bloc resection but results in perforation more often than does endoscopic mucosal resection. We report a novel technique of ESD using an external grasping forceps. A total of 265 lesions with EGC or gastric adenoma were enrolled in this study. Sixteen lesions were located in the upper third portion of the stomach, 114 in the middle third portion, and 135 in the lower third portion. After submucosal injection followed by circumcision of the lesions with a flex knife, the external grasping forceps was introduced with the help of a second grasping forceps and anchored at the margin of the lesion. Oral traction applied with this forceps could elevate the lesion and make the submucosal layer wider and more visible, thereby facilitating dissection of the submucosal layer under direct vision. The mean lesion size was 15.0 mm (range: 5–50 mm). All but 11 lesions (95.8%) could be resected en bloc with free margins. Mean procedure time was 45 min (range: 20–180 min). It was difficult to carry out this procedure when the lesions were located in the cardia, lesser curvature, or posterior wall of the upper third of the gastric body. Bleeding after ESD occurred in 10 patients (3.8%) and perforation occurred in one patient (0.4%). The endoscopic submucosal dissection using an external grasping forceps for superficial gastric neoplasia is efficacious and safe.     

SUCCESSFUL ENDOSCOPIC SUBMUCOSAL DISSECTION FOR MUCOSAL CANCER OF THE DUODENUM

We report a case of mucosal duodenal cancer in a 62‐year‐old woman, which was successfully removed en bloc by endoscopic submucosal dissection (ESD). The patient underwent an upper gastrointestinal endoscopy at our hospital, which revealed an elevated flat mucosal lesion (type IIa) measuring 10 mm in diameter in the second portion of the duodenum. Histopathological examination of a biopsy specimen revealed features suggestive of a tubulovillous adenoma with severe atypia. As the findings suggested that the lesion had an adenocarcinoma component but was confined to the mucosal layer, we decided to carry out ESD and successfully removed the tumor in one piece. The resected tumor was 20 × 15 mm in size. Histopathological examination revealed that the lesion was a well‐differentiated mucosal adenocarcinoma with no lymphovascular invasion. Mucosal duodenal cancer is extremely rare, and ESD of a lesion in the duodenum requires a high level of skill. To the best of our knowledge, this case is the first report of successful ESD carried out in a case of mucosal duodenal cancer.     

FEASIBILITY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR PATIENTS WITH CHRONIC RENAL FAILURE ON HEMODIALYSIS

Background: Endoscopic submucosal dissection (ESD) is expected as a curative method for node‐negative gastrointestinal cancers. Little is known about ESD for patients with end‐stage chronic renal failure (CRF) on hemodialysis. We aimed to evaluate the efficacy and safety of ESD for patients with CRF on hemodialysis. Methods: Ten consecutive patients with 12 lesions who underwent ESD (stomach, seven; colorectum, three) between March 2002 and August 2007 were retrospectively investigated in terms of the technical feasibility and complications. Results: All the lesions were resected in a single piece and en‐bloc and R0 resection rate was 100%. Histology revealed that all the lesions fulfilled the criteria of node‐negative cancers. Delayed bleeding requiring blood transfusion on the day after ESD, and shunt occlusion, which necessitated a radiological intervention 7 days after ESD, occurred in one stomach case. Delayed perforation followed by emergency surgery 2 days after ESD occurred in one colorectal case. Conclusions: ESD for CRF patients may be technically feasible, but substantial risks should be considered. Early detection of late‐onset complications is essential with intensive medical check‐up for at least 1 week in order to prevent complications from becoming severe.     

LOW‐FREQUENCY OF BACTEREMIA AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION OF THE STOMACH

Background: Mainstream therapy for early gastric cancer in Japan has now shifted from endoscopic mucosal resection (EMR) to endoscopic submucosal dissection (ESD). Although bacteremia is reported as being infrequent and transient in gastric EMR, there are no reports of it being investigated in gastric ESD. This study aimed to determine the frequency of bacteremia in gastric ESD. Patients and Methods: A prospective study, in 46 consecutive patients who underwent gastric ESD, investigated the frequency of bacteremia before and after the procedure. Results: The median time for the total ESD procedure was 105 min (range 30–400). The median volume of the submucosal injection was 80 ml (range 20–260). The mean size of the resected specimen was 40 ± 9.7 mm. Blood cultures obtained before ESD were positive in 4.4% (2/45) of cases. Bacillus subtilis and Bacillus spp. were the isolated microorganisms. Blood cultures obtained 10 min after ESD were positive in 4.3% (2/46) of cases; with the same microorganisms being isolated. Blood cultures obtained 3 h after ESD were all negative. No signs of sepsis were seen in the two patients with a positive blood culture 10 min after ESD. Conclusions: The frequency of bacteremia after gastric ESD was low and transient. ESD for gastric lesions is thought to have a low risk of infectious complications; therefore, prophylactic administration of antibiotics may not be warranted.     

CARBON DIOXIDE SUBMUCOSAL INJECTION CUSHION: AN INNOVATIVE TECHNIQUE IN ENDOSCOPIC SUBMUCOSAL DISSECTION

Aim: Endoscopic submucosal dissection (ESD) can successfully resect large lesions en bloc, but it requires a satisfactory submucosal (sm) injection agent for proper safety and efficacy. The aim of the present study was to evaluate the effectiveness of carbon dioxide (CO₂) as an ESD sm injection agent. Methods: In vitro study using porcine stomachs compared CO₂ with normal saline (NS) and sodium hyaluronic acid (SHA) solution, both of which are currently used to provide long‐lasting sm elevation during ESD. Histopathological examination assessed differences between CO₂ and NS sm cushions. ESD were then carried out in vivo in the stomach and rectum of a live pig using CO₂ sm injection. Results: CO₂ sm elevation was significantly longer lasting than either NS or SHA (P < 0.001). Histopathology revealed no mucosal layer tissue damage, and dissection of honeycomb‐like fibrous connective tissue in the CO₂ sm cushion. Creating and maintaining a CO₂ sm cushion of sufficient elevation combined with partial physical dissection of the sm layer was achieved, followed by complete endoscopic dissection of the sm layer with all ESD, resulting in successful en‐bloc resections having a mean specimen size of 24.3 mm within 15 min. Conclusion: Safety and efficacy of CO₂ as a satisfactory sm injection agent during ESD was successfully demonstrated in these preliminary studies, warranting further investigation of this innovative technique.     

EN BLOC REMOVAL OF A GASTRIC CARCINOID TUMOR USING ENDOSCOPIC SUBMUCOSAL DISSECTION TECHNIQUES

Endoscopic submucosal dissection (ESD) has recently been applied to the resection of gastric submucosal tumors other than carcinoid tumors. We describe a case of gastric carcinoid tumor enucleated with ESD. An 82‐year‐old woman was referred for treatment of a gastric tumor. Upper gastrointestinal endoscopy revealed a solitary submucosal tumor in the greater curvature of the gastric body. We diagnosed a carcinoid tumor by histological examination of biopsy specimens. Endoscopic ultrasound revealed a hypoechoic mass in the submucosal layer. Neither lymph node nor liver metastasis was recognized. The serum gastrin level was normal, and this tumor was classified as a type III (sporadic) carcinoid tumor. Endoscopic resection was decided on considering her age, general status, and wishes. We used ESD techniques, because the tumor was too large to be resected by conventional endoscopic mucosal resection. En bloc resection was performed. Histological examination of the 13 × 19 × 11 mm resected specimen showed that the cut end was free of tumor cells. Type III carcinoid tumor is usually treated by surgical resection with lymph node dissection. However, in high‐risk elderly patients we consider ESD to be a therapeutic option for local control of gastric carcinoid tumors.     

SUCCESSFUL ENDOSCOPIC CLOSURES OF COLONIC PERFORATIONS REQUIRING ABDOMINAL DECOMPRESSION AFTER ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY COLON CANCER

Endoscopic submucosal dissection (ESD) for colorectal cancer is not widely accepted because of its technical difficulty and the risk of perforation. In addition, the risk of peritonitis cannot be completely eliminated even if a perforation is closed successfully. Reported here are two cases of early colon cancer in which the patients sustained iatrogenic perforations of the ascending colon during conventional endoscopic mucosal resection and of the sigmoid colon during ESD, respectively, requiring abdominal decompression with an 18 G Medicut needle. Both of these perforations were successfully treated by endoscopic clipping. In conclusion, conservative medical management may be possible in patients who have undergone successful closure of colonic perforations using endoscopic clipping. In order to perform immediate endoscopic closure, abdominal decompression has been useful to decrease patient discomfort and colonic lumen collapse. Now, CO₂ insufflation is being used effectively for the prevention of pneumoperitoneum.     

ENDOSCOPIC SUBMUCOSAL DISSECTION (TWO‐POINT FIXED ESD) FOR EARLY ESOPHAGEAL CANCER

Background: We have been attempting to improve the safety, reliability and simplicity of endoscopic submucosal dissection for the treatment of early esophageal cancer and to shorten the time needed for this operation. Methods: The present study involved nine patients with well‐differentiated intramucosal early esophageal cancer over 20 mm in diameter. Two‐point fixed endoscopic submucosal dissection was carried out. Results: In all nine cases, the mucosal area to be dissected was successfully identified and kept under direct vision, allowing two‐point fixation of the mucosa with forceps and the hood during adequate counter‐traction. In this way, the respiration‐caused movement of submucosal tissue between the two fixing points was suppressed almost completely. Hemostasis and manipulation on blood vessels were easy with this procedure and dissection could be completed safely, without causing perforation. Conclusion: Endoscopic submucosal dissection with a transparent hood fitted with a mucosa‐holding forceps channel is highly useful, safe and simple when applied to the esophagus.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL SQUAMOUS CELL NEOPLASMS

Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard treatments for early esophageal cancer, as well as for early gastric cancer in Japan, but standardization of the knowledge is still incomplete. The final goal to perform ESD is not to resect the lesion in an en bloc fashion, but to save the patient from esophageal cancer‐related death. Thus, the indications should be considered based on the entire patient, not just the target lesion itself, and pre‐, peri‐ and postoperative management of the patient is also very important, as well as technical aspects of ESD. In terms of the techniques of ESD, owing to refinement of the procedural strategy, invention of the devices, and the learning curve, acceptable safety and favorable middle‐term efficacy have been obtained. We believe that ESD will become a standard treatment for early esophageal cancer not only in Japan but also worldwide in the near future.     

HEMOSTASIS WITH HOOK KNIFE DURING ENDOSCOPIC SUBMUCOSAL DISSECTION

Major complications reported with endoscopic submucosal dissection are bleeding and perforation. The most important step in preventing such complications is to maintain visualization of the submucosal layer. The hook knife is not only a useful cutting device for submucosal dissection, but the device also provides effective means for hemostasis and prevention of bleeding during endoscopic submucosal dissection. Vessels with a diameter of 1 mm or less do not bleed if cut with a hook knife using spray mode coagulation.     

USE OF SHORT NEEDLE KNIFE FOR ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION

Background: The emergence of endoscopic submucosal dissection (ESD) has enabled en bloc resection of lesions, which were conventionally difficult. However, ESD has problems of technical difficulty and high incidence of complications. In order to improve the procedure of marking and submucosal dissection in the esophagus, we modified and adjusted the standard needle knife to a short needle knife having a tip portion with a projection length of 1.5 mm. Methods: We treated 20 esophageal lesions with ESD using the short needle knife. We marked around the lesion with the short needle knife and performed mucosal incision of the entire circumference with a needle knife and an IT knife, then dissected the submucosal layer with the short needle knife. A Hook knife was also used in situations where muscular layers were located in the front‐view Results: Complete en bloc resection was performed in all 20 cases. The diameter of lesions ranged from 3 to 65 mm (median, 20 mm), and that of resected specimens ranged from 28 to 90 mm (median, 47 mm). Submucosal dissection was completed with the short needle knife alone in 13 cases in 20 (65%), and in seven cases (35%), in combination with so‐called Hook knife. The procedure was complicated in one patient with mediastinal emphysema. Conclusions: The short needle knife proved to be useful and safe in clear marking and submucosal dissection of esophageal lesions. It allows greater flexibility in the angle of insertion, and enables more effective and safer procedures because its full length can be inserted into the submucosa and fixed.     

RISK MANAGEMENT IN ENDOSCOPIC SUBMUCOSAL DISSECTION USING NEEDLE KNIFE IN KOREA

The needle knife is used for mucosal incision during endoscopic mucosal resection (EMR). The first author has used the needle knife for EMR since 1996 to overcome several limitations. Conventional EMR is not able to be used to remove tumors >15 mm. Excessive burning effect on the margin during strip biopsy leads to misdiagnosis during evaluation of resection margins. Relatively larger specimens could be resected and resection margins evaluated effectively with EMR with needle knife. Nowadays the needle knife is used to perform endoscopic submucosal dissection (ESD) from mucosal incision to submucosal dissection. The advantages of needle knife are as follows: (i) the lumen of the stomach can be kept clear during the whole procedure because of less burning effect; (ii) the procedure time for ESD is short because the needle knife has a very thin body, enabling the mucosal and submucosal layer to be cut quickly; and (iii) the needle knife can provide cutting action with the tip. In contrast, the needle knife has a high potential to cause perforation during incision and dissection. Only experts can use the needle knife safely. The perforated site can be closed endoscopically using hemoclips. To prevent perforation the needle knife should be kept parallel to the gastric wall during dissection. In conclusion, the needle knife has many advantages as well as a higher risk of perforation. However, the success rate for ESD using the needle knife increases with sufficient experience.