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Holmium Laser Assisted Mucosectomy (HLAM)
Abstracts Submitted to ASGE 2004 **180 Holmium Laser Assisted Mucosectomy (HLAM) Charles Dye, Timothy Kinney, Kenneth Chi, Irving Waxman
Naomi Kakushima, Naohisa Yahagi, Mitsuhiro Fujishiro, Atsushi Imagawa, Masashi Oka, Katsuya Kobayashi, Takuhei Hashimoto, Touru Motoi, Masao Omata
Endoscopic mucosal resection (EMR) is difficult for larger lesions, often resulting in piecemeal removal and incomplete resection. Adjunctive tools including insulated tip knives have been employed to facilitate larger and more complete resections, but use of these devices is technically demanding. Holmium laser systems are used widely in endoluminal urologic applications and allow only a limited depth of cut, potentially making these laser systems ideal for gastrointestinal mucosectomy. Aims: Preclinical study in a porcine model to demonstrate technical feasibility and safety of HLAM in various regions of the gastrointestinal tract. Materials and Methods: Two 30-50 kg pigs were studied in accordance with institutional protocol. A 360 um flexible laser fiber powered by a 30 Watt Holmium laser generator was passed through the accessory channel of dual channel endoscope and used to resect segments of esophageal, gastric, and colonic mucosa. Resections were performed with and without hydroxypropyl methycellulose injections for durable submucosal cushions. 2-4 cm ‘‘lesions’’ were created by the tip of a cautery snare. After laser dissection of the lesion boundaries, spontaneous tissue retraction facilitated tissue removal using snare cautery resection and forceps-assisted laser resection. Specimens were sent for histologic analysis. Results: Laser fibers were employed relatively easily and facilitated large en-block mucosectomies. The depth of penetration of the laser was limited to less than 4 mm at power settings up to 30 watts. It was not possible to perforate through the thicker muscle layers of the porcine esophagus and stomach despite intentional sustained discharge in one focal location. Perforation could be induced in the colon when submucosal injections were not employed for a cushion effect. Bleeding was infrequently noted, but treatable with the laser by defocusing the energy, or moving the fiber away from the target by 2-3 mm, thereby applying thermal energy as opposed to cutting energy. Conclusions: HLAM is technically feasible and offers advantages over techniques such as insulated tip knife assisted mucosectomy including relative ease of use, less risk of perforation, and immediate hemorrhage control. Potential applications include facilitating complete resection of larger lesions and and a less morbid alternative than photodynamic therapy for Barrett’s esophagus with advanced neoplasia.
Background & Aim: We have previously reported that gastric artificial ulcers after endoscopic submucosal dissection (ESD) heal within 8 weeks regardless of size and its location. Chronological endoscopic observation revealed that the ulcer size became nearly half of the previous size around 4 weeks after endoscopic resection. To clarify the healing process of post-ESD ulcers histopathologically, specimens from patients who underwent additional gastrectomy after ESD were studied. Method: Among 89 patients who were treated by ESD at the University of Tokyo Hospital from December 2001 to June 2003, 13 patients underwent additional surgery because of submucosal invasion and/or lymphovascular involvement proven by histological evaluation of the endoscopically resected specimen. Their resected stomach were subjected to assessment. Mean interval between ESD and additional gastrectomy was 7 weeks (range 1 to 17 weeks). Using the surgically resected specimens, the ulcer size, scar formation, appearance of regenerative mucosa and the extent of fibrosis were evaluated. Result: The average specimen size removed by ESD was 42.2 mm (range 20 to 60 mm). Two patients underwent surgery within 2 weeks after ESD, both of which showed marked fibrosis extending to the proper muscle layer with regional wall thickness, but regenerative mucosa hardly appeared. Among 6 patients who underwent surgery after 5 to 7 weeks, there was no wall thickness under the ulcer, and regenerative mucosa was observed at the ridge of the ulcer in 5 patients. In 4 patients, scar formation and fibrosis was observed with fusion of muscularis mucosa and proper muscle layer. Among 5 patients who underwent gastrectomy later than 8 weeks, mucosal defect was still observed in 2 cases. These 2 patients had severe fibrosis with the lesion due to previous peptic ulcer or submucosal invasion of the lesion. Conclusion: The remarkable size reduction of artificial ulcers after ESD occurs mainly by tissue contraction during the early period of the healing process. Then, regenerative mucosa extends from the rim of the ulcer to cover the mucosal defect left within 8 weeks. Even large post-ESD ulcers will heal within 8 weeks contributed mostly by the early period of the healing process. However, if fibrosis is suspected under the lesion before ESD, there is a possibility that the artificial ulcer will not heal within 8 weeks.
**181 Endoscopic Mucosal Resection (EMR) Using the Insulation-Tipped Diathermic Knife (IT Knife) Allows Curative Resection of Residual or Recurrent Gastric Cancer After EMR Chizu Yokoi, Takuji Gotoda, Roy M. Soetikno, Hisanao Hamanaka, Ichiro Oda Background: Repeat EMR to cure local recurrence of gastric cancer is difficult to perform because the initial EMR causes submucosal fibrosis. In turn, submucosal fibrosis causes the commonly used EMR techniques (strip biopsy, ligation, and cap techniques), to be performed piecemeal. Pathological evaluations of piecemealresected specimen are often ‘unable to be evaluated’ and thus leading patients to undergo additional palliative therapy such as APC or laser therapy. Without proper staging information, patients may also undergo unnecessary surgery. Newer technique of EMR using the IT knife (EMR-IT) allows submucosal dissection through the fibrosis and thus providing an en-bloc resection. We studied the safety and efficacy of EMR-IT and compared the results to historical controls. Methods: We used our prospectively entered database (1993 to 2003) to identify all patients who had locally recurrent gastric cancers that were treated with repeat EMR. We defined the resections as curative when the lateral and vertical margins were free of cancer. We recommended surgery when resection margin could not be evaluated to be free of cancer or there was submucosal invasion and/or vessel involvement. We used the Fisher’s exact test for statistical analysis. Results: Among 61 recurrent gastric cancers, 38 cancers were resected completely in one piece. 43 patients had EMR-IT and 18 had other conventional procedures. EMR-IT led to en-bloc resected specimen in 38 patients (88.4%) as compared to in 0 patient (0%) in other conventional procedures (P < 0.0001). Non-evaluable specimen was only 1 lesion (2.6%) in the total 38 en-bloc resections compared with 10 lesions (43.8%) in the total 23 piecemealed-resection (P < 0.0001). 3 residual tumors (30%) were found in the total 10 non-evaluable specimens. There was no evidence of additional recurrence in curative group (en-bloc;30, peacemeal; 9 lesions) or distant metastasis among the patients who underwent curative EMR during a follow-up period of median 25 months (range; 6 to 68 months). There were 3 perforations by EMR-IT; all were successfully treated endoscopically using the endoclips. Conclusions: EMR-IT allows curative resection of local recurrent gastric cancer after EMR, and allows resections to be performed through submucosal fibrosis and provides en-bloc specimen. In turn, en-bloc resections allow precise staging and prevent residual disease/recurrence.
**183 Endoscopic Ultrasonography (EUS) and Endoscopic Mucosal Resection (EMR) for Staging and Treatment of High-Grade Dysplasia (HGD) and Early Adenocarcinoma (EAC) in Barrett's Esophagus (BE) Charles J. Lightdale, Alberto Larghi, Heidrun Rotterdam, Nnenna Okpara Aim: Endoscopic therapy can be curative for BE and HGD (Tis) or EAC confined to the mucosa (T1m). The risk of lymph node metastasis increases with the depth of mucosal invasion, and rises rapidly with submucosal invasion (T1sm). EUS has provided the highest accuracy for clinical staging of depth of invasion, but remains imperfect. We tested a staging strategy of an initial EUS, followed by EMR in patients with #T1m on EUS. Methods: We staged patients with HGD or EAC with high-frequency EUS (20 MHz). Patients with EUS stage of $T1sm were referred to surgery. Patients with EUS stage #T1m had cap-assisted EMR of focal lesions in long-segment BE or of all short segment BE. EMR specimens were evaluated by histology: m1 = tumor above the basement membrane (HGD); m2 = tumor invading the lamina propria; m3 = tumor invading the muscularis mucosae; sm = tumor invading the submucosa. Results: A total of 50 patients (40 M, 10 F), mean age 70 years (range 36-87 years) with HGD and possible EAC in BE were evaluated with EUS. In 8 patients, EUS indicated $T1sm. EUS was accurate compared to surgical pathology in 7/8 cases, but over-staged 1 patient with T1m disease. EMR was carried out in the remaining 42 patients (20 focal lesions, 22 short segment BE). EMR staging results compared with initial endoscopic biopsy diagnosis are shown in the table below. EMR was carried out as an outpatient procedure without serious complication. Subsequent treatment was based on EMR results and clinical status. In the 22 patients with m1 (HGD) on EMR, 1 had esophagectomy, and 21 had endoscopic follow-up, including 6 who received additional endoscopic therapy (EMR, photodynamic therapy, or argon plasma coagulation). None of the 21 developed metastatic cancer over a mean of 15.4 6 9.0 months. In the 20 patients with EAC on EMR, 6 had esophagectomy, including 5/6 with sm invasion. In 12/14 patients, additional endoscopic therapy was carried out, and 1 patient received combined radiation and chemotherapy. None of the 14 developed metastatic cancer over a mean of 19.7 6 8.9 months. Conclusions: Staging patients with HGD and EAC in BE can be performed accurately with EUS followed by EMR. Invasion of the deep mucosa and the submucosa can be definitively established. In mediumterm follow-up, endoscopic therapy has been successful in patients with HGD and cancer limited to the mucosa.
**182 The Healing Process of Gastric Artificial Ulcers After Endoscopic Submucosal Dissection, a Histopathological Study P90
GASTROINTESTINAL ENDOSCOPY
VOLUME 59, NO. 5, 2004
Naomi Kakushima, Naohisa Yahagi, Mitsuhiro Fujishiro, Atsushi Imagawa, Masashi Oka, Katsuya Kobayashi, Takuhei Hashimoto, Touru Motoi, Masao Omata
Endoscopic mucosal resection (EMR) is difficult for larger lesions, often resulting in piecemeal removal and incomplete resection. Adjunctive tools including insulated tip knives have been employed to facilitate larger and more complete resections, but use of these devices is technically demanding. Holmium laser systems are used widely in endoluminal urologic applications and allow only a limited depth of cut, potentially making these laser systems ideal for gastrointestinal mucosectomy. Aims: Preclinical study in a porcine model to demonstrate technical feasibility and safety of HLAM in various regions of the gastrointestinal tract. Materials and Methods: Two 30-50 kg pigs were studied in accordance with institutional protocol. A 360 um flexible laser fiber powered by a 30 Watt Holmium laser generator was passed through the accessory channel of dual channel endoscope and used to resect segments of esophageal, gastric, and colonic mucosa. Resections were performed with and without hydroxypropyl methycellulose injections for durable submucosal cushions. 2-4 cm ‘‘lesions’’ were created by the tip of a cautery snare. After laser dissection of the lesion boundaries, spontaneous tissue retraction facilitated tissue removal using snare cautery resection and forceps-assisted laser resection. Specimens were sent for histologic analysis. Results: Laser fibers were employed relatively easily and facilitated large en-block mucosectomies. The depth of penetration of the laser was limited to less than 4 mm at power settings up to 30 watts. It was not possible to perforate through the thicker muscle layers of the porcine esophagus and stomach despite intentional sustained discharge in one focal location. Perforation could be induced in the colon when submucosal injections were not employed for a cushion effect. Bleeding was infrequently noted, but treatable with the laser by defocusing the energy, or moving the fiber away from the target by 2-3 mm, thereby applying thermal energy as opposed to cutting energy. Conclusions: HLAM is technically feasible and offers advantages over techniques such as insulated tip knife assisted mucosectomy including relative ease of use, less risk of perforation, and immediate hemorrhage control. Potential applications include facilitating complete resection of larger lesions and and a less morbid alternative than photodynamic therapy for Barrett’s esophagus with advanced neoplasia.
Background & Aim: We have previously reported that gastric artificial ulcers after endoscopic submucosal dissection (ESD) heal within 8 weeks regardless of size and its location. Chronological endoscopic observation revealed that the ulcer size became nearly half of the previous size around 4 weeks after endoscopic resection. To clarify the healing process of post-ESD ulcers histopathologically, specimens from patients who underwent additional gastrectomy after ESD were studied. Method: Among 89 patients who were treated by ESD at the University of Tokyo Hospital from December 2001 to June 2003, 13 patients underwent additional surgery because of submucosal invasion and/or lymphovascular involvement proven by histological evaluation of the endoscopically resected specimen. Their resected stomach were subjected to assessment. Mean interval between ESD and additional gastrectomy was 7 weeks (range 1 to 17 weeks). Using the surgically resected specimens, the ulcer size, scar formation, appearance of regenerative mucosa and the extent of fibrosis were evaluated. Result: The average specimen size removed by ESD was 42.2 mm (range 20 to 60 mm). Two patients underwent surgery within 2 weeks after ESD, both of which showed marked fibrosis extending to the proper muscle layer with regional wall thickness, but regenerative mucosa hardly appeared. Among 6 patients who underwent surgery after 5 to 7 weeks, there was no wall thickness under the ulcer, and regenerative mucosa was observed at the ridge of the ulcer in 5 patients. In 4 patients, scar formation and fibrosis was observed with fusion of muscularis mucosa and proper muscle layer. Among 5 patients who underwent gastrectomy later than 8 weeks, mucosal defect was still observed in 2 cases. These 2 patients had severe fibrosis with the lesion due to previous peptic ulcer or submucosal invasion of the lesion. Conclusion: The remarkable size reduction of artificial ulcers after ESD occurs mainly by tissue contraction during the early period of the healing process. Then, regenerative mucosa extends from the rim of the ulcer to cover the mucosal defect left within 8 weeks. Even large post-ESD ulcers will heal within 8 weeks contributed mostly by the early period of the healing process. However, if fibrosis is suspected under the lesion before ESD, there is a possibility that the artificial ulcer will not heal within 8 weeks.
**181 Endoscopic Mucosal Resection (EMR) Using the Insulation-Tipped Diathermic Knife (IT Knife) Allows Curative Resection of Residual or Recurrent Gastric Cancer After EMR Chizu Yokoi, Takuji Gotoda, Roy M. Soetikno, Hisanao Hamanaka, Ichiro Oda Background: Repeat EMR to cure local recurrence of gastric cancer is difficult to perform because the initial EMR causes submucosal fibrosis. In turn, submucosal fibrosis causes the commonly used EMR techniques (strip biopsy, ligation, and cap techniques), to be performed piecemeal. Pathological evaluations of piecemealresected specimen are often ‘unable to be evaluated’ and thus leading patients to undergo additional palliative therapy such as APC or laser therapy. Without proper staging information, patients may also undergo unnecessary surgery. Newer technique of EMR using the IT knife (EMR-IT) allows submucosal dissection through the fibrosis and thus providing an en-bloc resection. We studied the safety and efficacy of EMR-IT and compared the results to historical controls. Methods: We used our prospectively entered database (1993 to 2003) to identify all patients who had locally recurrent gastric cancers that were treated with repeat EMR. We defined the resections as curative when the lateral and vertical margins were free of cancer. We recommended surgery when resection margin could not be evaluated to be free of cancer or there was submucosal invasion and/or vessel involvement. We used the Fisher’s exact test for statistical analysis. Results: Among 61 recurrent gastric cancers, 38 cancers were resected completely in one piece. 43 patients had EMR-IT and 18 had other conventional procedures. EMR-IT led to en-bloc resected specimen in 38 patients (88.4%) as compared to in 0 patient (0%) in other conventional procedures (P < 0.0001). Non-evaluable specimen was only 1 lesion (2.6%) in the total 38 en-bloc resections compared with 10 lesions (43.8%) in the total 23 piecemealed-resection (P < 0.0001). 3 residual tumors (30%) were found in the total 10 non-evaluable specimens. There was no evidence of additional recurrence in curative group (en-bloc;30, peacemeal; 9 lesions) or distant metastasis among the patients who underwent curative EMR during a follow-up period of median 25 months (range; 6 to 68 months). There were 3 perforations by EMR-IT; all were successfully treated endoscopically using the endoclips. Conclusions: EMR-IT allows curative resection of local recurrent gastric cancer after EMR, and allows resections to be performed through submucosal fibrosis and provides en-bloc specimen. In turn, en-bloc resections allow precise staging and prevent residual disease/recurrence.
**183 Endoscopic Ultrasonography (EUS) and Endoscopic Mucosal Resection (EMR) for Staging and Treatment of High-Grade Dysplasia (HGD) and Early Adenocarcinoma (EAC) in Barrett's Esophagus (BE) Charles J. Lightdale, Alberto Larghi, Heidrun Rotterdam, Nnenna Okpara Aim: Endoscopic therapy can be curative for BE and HGD (Tis) or EAC confined to the mucosa (T1m). The risk of lymph node metastasis increases with the depth of mucosal invasion, and rises rapidly with submucosal invasion (T1sm). EUS has provided the highest accuracy for clinical staging of depth of invasion, but remains imperfect. We tested a staging strategy of an initial EUS, followed by EMR in patients with #T1m on EUS. Methods: We staged patients with HGD or EAC with high-frequency EUS (20 MHz). Patients with EUS stage of $T1sm were referred to surgery. Patients with EUS stage #T1m had cap-assisted EMR of focal lesions in long-segment BE or of all short segment BE. EMR specimens were evaluated by histology: m1 = tumor above the basement membrane (HGD); m2 = tumor invading the lamina propria; m3 = tumor invading the muscularis mucosae; sm = tumor invading the submucosa. Results: A total of 50 patients (40 M, 10 F), mean age 70 years (range 36-87 years) with HGD and possible EAC in BE were evaluated with EUS. In 8 patients, EUS indicated $T1sm. EUS was accurate compared to surgical pathology in 7/8 cases, but over-staged 1 patient with T1m disease. EMR was carried out in the remaining 42 patients (20 focal lesions, 22 short segment BE). EMR staging results compared with initial endoscopic biopsy diagnosis are shown in the table below. EMR was carried out as an outpatient procedure without serious complication. Subsequent treatment was based on EMR results and clinical status. In the 22 patients with m1 (HGD) on EMR, 1 had esophagectomy, and 21 had endoscopic follow-up, including 6 who received additional endoscopic therapy (EMR, photodynamic therapy, or argon plasma coagulation). None of the 21 developed metastatic cancer over a mean of 15.4 6 9.0 months. In the 20 patients with EAC on EMR, 6 had esophagectomy, including 5/6 with sm invasion. In 12/14 patients, additional endoscopic therapy was carried out, and 1 patient received combined radiation and chemotherapy. None of the 14 developed metastatic cancer over a mean of 19.7 6 8.9 months. Conclusions: Staging patients with HGD and EAC in BE can be performed accurately with EUS followed by EMR. Invasion of the deep mucosa and the submucosa can be definitively established. In mediumterm follow-up, endoscopic therapy has been successful in patients with HGD and cancer limited to the mucosa.
**182 The Healing Process of Gastric Artificial Ulcers After Endoscopic Submucosal Dissection, a Histopathological Study P90
GASTROINTESTINAL ENDOSCOPY
VOLUME 59, NO. 5, 2004