MANAGEMENT OF BLEEDING CONCERNING ENDOSCOPIC SUBMUCOSAL DISSECTION WITH THE FLEX KNIFE FOR STOMACH NEOPLASM

Management of bleeding is crucial for a successful endoscopic submucosal dissection (ESD) with the Flex knife for a stomach neoplasm. Medical approaches to suppress gastric acid secretion and keep systolic blood pressure at the level of < 150 mmHg during ESD are tried to lessen bleeding. But, major concerns for bleeding are whether the blood vessels are cut off or not and endoscopic surgeons have to avoid blind application of devices for ESD as much as possible. Even in the situations where blind application for non‐visible vessels in the submucosa is not preventable such as in the steps of marking, submucosal injection, mucosal incision, and snaring, the efforts to lessen bleeding are necessary. When non‐bleeding visible vessels are noticed, ‘prebleeding coagulation’ with appropriate devices is important. Even if unexpected bleeding occurs, it is also controllable using appropriate devices according to the type of bleeding. All endscopists who perform ESD should also be experts in management of bleeding.     

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.     

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.     

NEW DEVICE TO PERFORM COAGULATION AND IRRIGATION SIMULTANEOUSLY DURING ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN INSULATION‐TIPPED ELECTROSURGICAL KNIFE

Background: Although bleeding is an unavoidable complication of endoscopic submucosal dissection (ESD), endoscopic hemostasis using an insulation‐tipped electrosurgical knife (IT) knife is impossible because an insulator is mounted at the tip of the knife. We have developed a new type of hood which could perform both coagulation and irrigation simultaneously. Methods: Our new device was fabricated by drilling a side hole in the cap portion of a conventional transparent hood followed by attaching a machined papillotomy knife to the exterior surface of the hole. Results: Our new hood was useful for hemorrhage during ESD using IT knife. Conclusions: With this method, endoscopic hemostasis using IT knife is easy, as hemostatic procedure can be performed under irrigation and coagulation using conventional endoscopy.     

RISK MANAGEMENT TO PREVENT PERFORATION DURING ENDOSCOPIC SUBMUCOSAL DISSECTION

En bloc resection is beneficial for accurate histological assessment of resected specimens of endoscopic mucosal resection. Conventional endoscopic mucosal resection is simple and convenient but with this procedure the size of specimen obtained from one‐piece resection is very limited. Endoscopic submucosal dissection (ESD) using IT knife, Hook knife, Flex knife and so on has already been reported and it is useful to some expert endoscopists, but sometimes difficult for general endoscopists to use safely. The drawback of ESD is that it is difficult and is consequently associated with a higher rate of perforation, which may reach up to 2–6% . In addition, ESD requires advanced endoscopic techniques. Further improvement of devices and techniques is expected to be developed to prevent perforation for ESD procedure.     

MANAGEMENT TO PREVENT BLEEDING DURING ENDOSCOPIC SUBMUCOSAL DISSECTION USING THE FLUSH KNIFE FOR GASTRIC TUMORS

The gastric vasculature responsible for intraoperative bleeding in endosocpic submucosal dissection (ESD) is the ramified vascular network occupying the middle of the submucosal layer and large vessels penetrating the muscle layer. Appropriate management for these vessels must be addressed. The trimming of the ramified vascular network can be safely performed with coagulation mode following shallow mucosal cutting. A large penetrating vessel usually requires precoagulation prior to dissection. These procedures are effectively performed with the water jet short needle knife (Flush knife).     

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.     

SEDATION WITH DEXMEDETOMIDINE HYDROCHLORIDE DURING ENDOSCOPIC SUBMUCOSAL DISSECTION OF GASTRIC CANCER

Aim: Although the treatment of early gastric cancer with endoscopic submucosal dissection (ESD) has been widely carried out, a standardized method of sedation for ESD has not been established. The purpose of the present study was to evaluate the efficacy and safety of sedation with dexmedetomidine (DEX). Methods: We conducted a randomized study involving 90 patients with gastric tumors who were intended to be treated with ESD. The patients were sedated either with DEX (i.v. infusion of 3.0 µg/kg per h over 5 min followed by continuous infusion at 0.4 µg/kg per h [n = 30]), propofol (PF [n = 30]), or midazolam (MDZ [n = 30]). In all groups, 1 mg MDZ was added i.v. as needed. Results: En bloc resection of the gastric tumor was achieved in 88 (98%) patients. None of the DEX‐sedated patients showed a significant reduction of the oxygen saturation level. The percentage of patients who showed body movement in the DEX group was significantly lower than those in the PF and MDZ groups, and the mean dose of additional MDZ in the DEX group was significantly smaller than that in the MDZ group. The rate of effective sedation was significantly higher in the DEX group compared with the MDZ or PF group. The mean length of ESD in the DEX group was 65 min, which was significantly shorter than in the other two groups. No DEX‐sedated patient developed major surgical complications. Conclusions: Sedation with DEX is effective and safe for patients with gastric tumors who are undergoing ESD.     

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.     

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.     

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.     

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.     

RARE GASTRIC CALCIFYING FIBROUS PSEUDOTUMOR REMOVED BY ENDOSCOPIC SUBMUCOSAL DISSECTION

We report a case of a calcifying fibrous pseudotumor of the stomach that we resected using endoscopic submucosal dissection (ESD). A 61‐year‐old male with a gastric submucosal tumor was admitted to our hospital for treatment. By upper gastrointestinal tract endoscopy, a smooth‐surfaced submucosal tumor measuring 2 cm in diameter was observed in the anterior wall of the middle body of the stomach. By endoscopic ultrasonography, a mass was observed in the stomach submucosa; the mass had a well‐defined boundary. Internally, the mass was heterogeneous and hypoechoic; high spots were scattered throughout the mass. Continuity between the mass and the muscularis mucosae and muscularis propria was not observed. Strongly suspecting that this mass was a gastrointestinal stromal tumor arising from the stomach, we resected the mass by ESD for total biopsy. Histopathologically, the mass consisted of proliferation of eosinophilic collagen fibers with plasma cell infiltration and lymphoid follicle proliferation. Calcification was also observed in some parts of the mass. Thus, the mass was identified as calcifying fibrous pseudotumor. Calcifying fibrous pseudotumor of the stomach is extremely rare and its histogenesis remains unclear; however, its morphology became distinct by comparing endoscopic/radiological and histopathological findings.     

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.     

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.     

THE HEALING PROCESS OF GASTRIC ARTIFICIAL ULCERS AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION

Background: Due to the remarkable progress of endoscopic resection techniques, endoscopic submucosal dissection (ESD) has been widely performed for larger mucosal tumors that would result in large arti?cial ulcers. The healing process of peptic ulcers has been previously studied in detail; however, no precise investigation for arti?cial ulcers after ESD has been reported. To con?rm the validity of the treatment from the aspect of wound healing, we aimed to clarify the healing process of large gastric arti?cial ulcers after ESD. Methods: Seventy patients with gastric mucosal tumors treated by ESD were enrolled. The size, location and time of scar formation of the ulcers were reviewed using endoscopic pictures taken from the same view and angle. Follow‐up endoscopy was performed at 1, 4, 8 and 12 weeks after ESD. For postoperative medication, all patients received normal doses of proton pump inhibitors and sucralfate for 8 weeks. Results: The average size of the resected specimen was 34.7 mm (20–90 mm). Irrespective of ulcer size and location, all of the cases healed up to scarring stages within 8 weeks. Conclusions: Gastric arti?cial ulcers after ESD healed within 8 weeks regardless of size and location using normal doses of medication as peptic ulcers. The fact that even giant ulcers after ESD heal within 8 weeks could be helpful information for candidates for ESD and for postoperative management of patients after ESD.     

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.     

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.     

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.