**2. Patients and methods**

From 1996 to 2005, 36 patients who had esophageal SCC with submucosal invasion underwent multimodal treatment. Esophagectomy was not performed because of associated complications in 19 cases and due to patient refusal in 17 cases.

In all patients, EMR/ESD was performed before any other treatment. Then chemotherapy, radiotherapy, or chemoradiotherapy was added, depending on the histopathological findings, which were classified according to the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus4). Submucosal invasion was classified into the following three grades: sm1: ≤200 μm, sm2: >200 μm, and sm2 EM (+): residual cancer cells at the resected margin.

In principle, radiotherapy or chemoradiotherapy was added if the resected margin was suspected to contain residual cancer cells, while chemotherapy was performed if lymphatic invasion was found in the resected specimen (Fig 1). Argon plasma coagulation was added without radiation if the residual tumor was limited to a small area.

#### **2.1 Method of EMR**

EMR was performed by the EEMR or EMRC method1)2). EMRC was done by using a singlechannel endoscope (GIF Q260; Olympus) with a cap (Olympus, Tokyo, Japan). After chromoendoscopy with iodine solution, saline was injected into the submucosal layer.

Combination Therapy After EMR/ESD for

CDDP (80mg/m2) 5FU (800mg/m2)

CDDP (70mg/m2) 5FU (700mg/m2)

**Chemotherapy**

**Chemoradiotherapy**

Fig. 2. Chemotherapy and chemoradiotherapy

Fig. 3. The radiation field was limited to local area

+ radiotherapy, and 10 had EMR + chemoradiotherapy.

**3. Results** 

Esophageal Squamous Cell Carcinoma with Submucosal Invasion 93

Day1-5 Day29-33

Day1-4 Day29-32

RT(1.8-2.0Gy/day)

There were no complications of EMR/ESD. On histopathological examination, the depth of tumor invasion was sm1 in 22 cases, sm2 in 9, and sm2 EM (+) in 5. Lymphatic invasion (ly)

Sixteen patients were treated with EMR alone, 8 received EMR + chemotherapy, 2 had EMR

was found in 18 cases (50%), and there was 1 case (3%) of vascular invasion (v).

Next, a snare (SD-7P, Olympus) was opened inside the cap, the tumor was aspirated into the cap, and the snare was closed. The forced coagulation mode was used to perform resection. EMMR was done by using a single-channel endoscope (GIF Q260; Olympus) fitted with an EEMR-tube. The method was same as that for EMRC until the injection of saline. Then a snare (SD-7P, Olympus) was passed through a side channel of the tube and was opened over the tumor. The tumor was aspirated into the tube using the suction of the endoscope and the snare was tightened. Resection was done in the forced coagulation mode.

Fig. 1. Fundamental clinical course

#### **2.2 Method of ESD**

A hook knife from Olympus (Tokyo, Japan) was used for the hook knife method of ESD3)5) along with a single-channel endoscope (GIF Q260; Olympus) and an attachment. The electrical generator was a VIO (ERBE, Tübingen, Germany). Before marking, chromoendoscopy with iodine solution was done to identify the lateral margins of the lesion. Then marking was undertaken in the hook knife using the forced coagulation mode. After 10% glycerin was injected into the submucosal, mucosal incision was performed in the endo cut mode. Before performing submucosal dissection, hyaluronic acid solution was injected into the submucosal lesion. Then the clip with thread was attached to the oral border of the specimen and the thread was pulled in the oral direction to exert traction on the submucosal layer. Next, the submucosal lesion was dissected off the muscle layer by using the hook knife in the endo cut mode. Bleeding was controlled with hemostatic forceps (FD-411QR; Olympus) in the soft coagulation mode or with the hook knife in the spray mode. ESD was performed with the patient under sedation by intravenous administration of diazepam and pentazocine as required plus continuous infusion of propofol.

#### **2.3 Chemotherapy and radiotherapy**

Chemotherapy was performed for 2 courses if lymphatic invasion was found in the resected specimen. Patients were principally given a combination of cisplatin/5-fluorouracil or nedaplatin/5-fluorouracil (Fig. 2). Radiotherapy was given to a total dose of 50-60 Gy, with the radiation field being limited to the local tumor area (Fig. 3).

Next, a snare (SD-7P, Olympus) was opened inside the cap, the tumor was aspirated into the cap, and the snare was closed. The forced coagulation mode was used to perform resection. EMMR was done by using a single-channel endoscope (GIF Q260; Olympus) fitted with an EEMR-tube. The method was same as that for EMRC until the injection of saline. Then a snare (SD-7P, Olympus) was passed through a side channel of the tube and was opened over the tumor. The tumor was aspirated into the tube using the suction of the endoscope and the snare was tightened. Resection was done in the forced coagulation

**ly(-)**

 **Follow up (EMR alone)**

**Chemotherapy**

**Chemoradiotherapy**

**Coagulation (APC)**

**Radiotherapy (RT)**

 **(CRT)**

**ly(+)**

**ly(-)**

A hook knife from Olympus (Tokyo, Japan) was used for the hook knife method of ESD3)5) along with a single-channel endoscope (GIF Q260; Olympus) and an attachment. The electrical generator was a VIO (ERBE, Tübingen, Germany). Before marking, chromoendoscopy with iodine solution was done to identify the lateral margins of the lesion. Then marking was undertaken in the hook knife using the forced coagulation mode. After 10% glycerin was injected into the submucosal, mucosal incision was performed in the endo cut mode. Before performing submucosal dissection, hyaluronic acid solution was injected into the submucosal lesion. Then the clip with thread was attached to the oral border of the specimen and the thread was pulled in the oral direction to exert traction on the submucosal layer. Next, the submucosal lesion was dissected off the muscle layer by using the hook knife in the endo cut mode. Bleeding was controlled with hemostatic forceps (FD-411QR; Olympus) in the soft coagulation mode or with the hook knife in the spray mode. ESD was performed with the patient under sedation by intravenous administration of

Chemotherapy was performed for 2 courses if lymphatic invasion was found in the resected specimen. Patients were principally given a combination of cisplatin/5-fluorouracil or nedaplatin/5-fluorouracil (Fig. 2). Radiotherapy was given to a total dose of 50-60 Gy, with

diazepam and pentazocine as required plus continuous infusion of propofol.

the radiation field being limited to the local tumor area (Fig. 3).

**ly(+)**

mode.

**Complete**

**EMR/ESD**

Fig. 1. Fundamental clinical course

**2.3 Chemotherapy and radiotherapy** 

**2.2 Method of ESD** 

**Incomplete**

Fig. 2. Chemotherapy and chemoradiotherapy

Fig. 3. The radiation field was limited to local area
