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 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.     

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 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 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.     

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.     

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.     

IS IT DIFFICULT FOR ENDOSCOPISTS WHO HAVE DONE CONVENTIONAL ENDOSCOPIC MUCOSAL RESECTION TO PERFORM SUBMUCOSAL DISSECTION?

Submucosal resection is a very useful method of endoscopic mucosal resection (EMR) for en bloc resection. We began using this method in March 2003 and have resected lesions in 16 patients with gastric cancer. We describe the procedure times and complications associated with submucosal resection from a beginner's point of view. Our first five patients experienced bleeding and perforation. With the aid of a range of instruments and the advice of expert endoscopists, our complication rate became very low and the procedure time much shorter. Endoscopists who seek to perform submucosal dissections easily and safely should avail themselves of training and education from experts in the method. A program for training endoscopists in submucosal dissection is essential.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER: TECHNICAL FEASIBILITY,OPERATION TIME AND COMPLICATIONS FROM A LARGE CONSECUTIVE SERIES

Background: Endoscopic mucosal resection (EMR) is a recognized treatment for early gastric cancer (EGC). One‐piece resection is considered to be a gold standard of EMR, as it provides accurate histological assessment and reduces the risk of local recurrence. Endoscopic submucosal dissection (ESD) is a new technique developed to obtain one‐piece resection even for large and ulcerative lesions. The present study aims to identify the technical feasibility, operation time and complications from a large consecutive series. Methods: We reviewed all patients with EGC who underwent ESD using the IT knife at National Cancer Center Hospital in the period between January 2000 and December 2003. Results: During the study period of 4 years we identified a total of 1033 EGC lesions in 945 consecutive patients who underwent ESD using the IT knife. We found a one‐piece resection rate (OPRR) of 98% (1008/1033). Our OPRR with tumor‐free margins was 93% (957/1033). On subgroup analysis it was found to be 86% (271/314) among large lesions (≥ 21 mm) and 89% (216/243) among ulcerative lesions. The overall non‐evaluable resection rate was 1.8% (19/1033). The median operation time was 60 min (range; 10–540 min). Evidence of immediate bleeding was found in 7%. Delayed bleeding after ESD was seen in 6% and perforation in 4% of the cases. All cases with complications except one were successfully treated by endoscopic treatment. Conclusion: The present study shows the technical feasibility of ESD, which provides one‐piece resections even in large and ulcerative EGC.     

NEW ENDOSCOPIC TECHNIQUE TO CLOSE LARGE MUCOSAL DEFECTS AFTER ENDOSCOPIC MUCOSAL RESECTION IN PATIENTS WITH GASTRIC MUCOSAL TUMORS

Endoscopic mucosal resection has been recognized as a standard method for treating mucosal tumors of the stomach in Japan. In our department, we have treated mucosal defects after this procedure by using metallic clips to prevent and manage complications related to endoscopic mucosal resection. In the present study, we explain the new technique, the ‘loop‐and‐clips’ method, which uses clips and a detachable snare to close large mucosal defects after endoscopic mucosal resection.     

PRESENT STATUS and PERSPECTIVES OF SUBMUCOSAL DISSECTING METHOD OF ENDOSCOPIC MUCOSAL RESECTION IN THE COLORECTUM IN JAPAN

Endoscopic mucosal resection (EMR) is one of the endoscopic procedures for treatment of intramucosal cancer of the gastrointestinal tract. This method enables complete resection of a lesion, however, the size of lesions which can be resected en bloc has a limit. For lesions which can not be resected en bloc, endoscopic piecemeal mucosal resection (EPMR) are employed. However, it is often difficult to determine cancer invasion at holizontal and vertical cut end on pathological examination of resected specimens. Therefore, for the purpose of en bloc resection submucosal dissecting method of endoscopic mucosal resection (SDEMR) that is a method by which mucosa is dissected using some special devices after circumferential mucosal incision around the lesion was proposed. It enables us to resect large lesions which cannot be removed en bloc by EMR. Therefore, it is possible that this procedure is able to prevent residual cancer. Furthermore, sufficient pathological examination of resected specimens is possible, and it helps to determine a therapeutic plan after resection. It is now widely accepted as one of the endoscopic procedures for treatment of early gastric cancer, however, there have been few reports on its experience in the colorectum. Then, in order to consider the perspectives of SDEMR in the colorectum, the present status of it in Japan in August 2003 was analyzed and reviewed in this paper.     

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.     

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.     

ADVANTAGES OF USING THIN ENDOSCOPE‐ASSISTED ENDOSCOPIC SUBMUCOSAL DISSECTION TECHNIQUE FOR LARGE COLORECTAL TUMORS

Background: Our purpose was to evaluate the effectiveness of a newly developed non‐invasive traction technique known as thin endoscope‐assisted endoscopic submucosal dissection (TEA‐ESD) procedure for the removal of colorectal laterally spreading tumors (LST). Patients and Methods: A total of 37 LST located in the rectum and distal sigmoid colons of 37 patients were eligible for outcome analysis. Twenty‐one LST were treated with TEA‐ESD and were then retrospectively compared to 16 LST that had previously been treated with standard ESD. Tumor size, en bloc resection rate, procedure time, combined number of different electrical surgical knives used during each procedure and associated complications were evaluated in this case–control study. Results: There was no statistically significant difference in tumor size between the TEA‐ESD group and the ESD control group (43.6 ± 16 mm and 42.4 ± 14 mm, respectively). All LST were successfully resected en bloc in both groups. Procedure duration was shorter for the TEA‐ESD group than the ESD control group, although the difference was not statistically significant (96 ± 53 minutes vs 116 ± 74 minutes; P = 0.18). The percentage of cases in which only one electrical surgical knife was used during the entire procedure was significantly higher in the TEA‐ESD group compared to the ESD control group (85.7% vs 31.3%; P = 0.0005). There were no perforations in the TEA‐ESD group while the ESD control group experienced one perforation. At the present time, TEA‐ESD is limited to the rectum and distal sigmoid colon. Conclusion: It was technically easier, safer and more cost‐effective to perform ESD for LST in the rectum and the distal sigmoid colon using the newly developed TEA‐ESD traction technique.     

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.     

MID‐TERM PROGNOSIS AFTER ENDOSCOPIC RESECTION FOR SUBMUCOSAL COLORECTAL CARCINOMA: SUMMARY OF A MULTICENTER QUESTIONNAIRE SURVEY CONDUCTED BY THE COLORECTAL ENDOSCOPIC RESECTION STANDARDIZATION IMPLEMENTATION WORKING GROUP IN JAPANESE SOCIETY FOR CANCER OF THE COLON AND RECTUM

We carried out a retrospective questionnaire survey of 792 submucosal colorectal carcinoma (CRC) cases from 15 institutions affiliated with the Colorectal Endoscopic Resection Standardization Implementation Working Group in Japanese Society for Cancer of the Colon and Rectum. In these cases, endoscopic resection (ER) and surveillance was carried out without additional surgical resection. Local recurrence or metastasis was observed in 18 cases. Local submucosal recurrence was observed in 11 cases, and metastatic recurrence was observed in 13 cases. Among the 15 cases in which the depth of submucosal invasion was measured, two cases showed depth less than 1000 µm, which has other risk factors for metastasis. Metastatic recurrence was observed in the lung, liver, lymph node, bone, adrenal glands, and the brain; in some cases, metastatic recurrence was observed in multiple organs. Death due to primary disease was observed in six cases. The average interval between ER and recurrence was 19.7 ± 9.2 months. In 16 cases, recurrence was observed within 3 years after ER. Thus, validity of ER without additional surgical resection for cases with the conditions that the depth of submucosal invasion is less than 1000 µm and the histological grade is well or moderately differentiated adenocarcinoma with no lymphatic and venous involvement was proven.     

RISK MANAGEMENT OF THERAPEUTIC COLONOSCOPY (HOT BIOPSY,POLYPECTOMY, ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION)

The concept of an adenoma–carcinoma sequence has been widely accepted in the colon and rectum, contrary to that in gastric cancer. Consequently, most target lesions for endoscopic resection using these newly developed techniques are histologically assessed as adenoma or intramucosal carcinoma in adenoma. Based on results in conventional endoscopic mucosal resection (EMR), almost all remnant or recurrent tumors can be successfully managed by salvage EMR, and all materials resected by salvage EMR also showed adenoma or intramucosal cancer. These results suggest that en bloc resection is not always clinically necessary to obtain complete cure for all colorectal neoplasia. However, larger lesions tend to be resected in a piecemeal fashion; it is difficult to confirm whether EMR has been completed or not. For precise histopathological assessment of the resected specimen, endoscopic submucosal dissection (ESD) for en bloc resection is desirable, although further experience is needed to establish its safety and efficacy. The present review contains a summary of the risk management of therapeutic colonoscopy including ESD for large colorectal mucosal neoplasia, debated at the Endoscopic Forum Japan 2006, Hakone, and discussion of the problems and future prospects of these procedures.     

INDICATIONS FOR ENDOSCOPIC MUCOSAL RESECTION FOR EARLY COLORECTAL CANCER: SHOULD THEY BE STRICT OR SHOULD THEY BE EXPANDED?

Endoscopic technologies have been developed greatly. As for early gastric cancer, the indications for endoscopic mucosal resection for early colorectal cancer have been widened recently. Technological advances can support wider and deeper resections using endoscopy but the remaining problem for the endoscopic management of cancer is lymph node metastasis. I discuss here the indication for endoscopic mucosal resection for early colorectal cancer to bring into focus the risk factors for metastasis to lymph nodes.     

ENDOSCOPIC RESECTION FOR EARLY GASTRIC CANCER AND FUTURE EXPECTATIONS

Considering the risks of surgery and the patient's poor quality of life after gastrectomy, it is sensible to offer endoscopic resection for the patients without risk of lymph node metastasis. Endoscopic resection (ER) of early gastric cancer (EGC) is now standard therapy in Japan and is increasingly becoming accepted and regularly used in other countries. The indications, techniques, and pathological assessment methods of ER in the treatment of EGC are demanding and require the endoscopist to follow them closely in order to ensure successful outcomes. New developments in ER techniques to dissect the submucosa directly, called ESD, allow resections of larger lesions in en‐bloc, although long‐term outcome data are currently still in progress. The purposes of the present review are to introduce ER methods for carrying out proper treatment and to describe future expectations.     

IMPACT OF ULTRASONOGRAPHY ON DIAGNOSIS OF T1 ESOPHAGEAL CANCER AS A CANDIDATE FOR ENDOSCOPIC MUCOSAL RESECTION

To get the correction information to decide whether endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) should be performed, endoscopic examinations, including multiple modalities such as chromoendoscopy, magnifying endoscopy and ultrasonography, are routinely performed in one or two sessions of endoscopic examination. Ultrasonography provides a cross sectional view of the tumor, which is useful information in the decision between EMR or surgery. The final treatment strategy should be decided according to the histological analysis of the resected specimen.