Histological study of the thin membranous dense connective tissues around the curving portion of the bilateral recurrent laryngeal nerves.

OBJECTIVE/AIM: We aimed to demonstrate the anatomical relationship between the recurrent laryngeal nerves (RLNs), thin membranous dense connective tissue (TMDCT [e.g., the visceral or vascular sheaths around the esophagus]), and the lymph nodes around the esophagus at the curving portion of the RLNs for rational and efficient lymph node dissection. METHODS: Transverse sections of the mediastinum at 5 mm or 1 mm intervals were obtained from four cadavers. Hematoxylin and eosin staining and Elastica van Gieson staining were performed. RESULTS: The visceral sheaths could not be clearly observed the curving portions of the bilateral RLNs, which were observed on the cranial and medial side of the great vessels (aortic arch and right subclavian artery [SCA]). The vascular sheaths could be clearly observed. The bilateral RLNs diverged from the bilateral vagus nerves, which ran along with the vascular sheaths, went up around the caudal side of the great vessels and the vascular sheath, and ran cranially on the medial side of the visceral sheath. Visceral sheaths were not observed around the region containing the left tracheobronchial lymph nodes (No. 106tbL) or the right recurrent nerve lymph nodes (No. 106recR). The regions containing the left recurrent nerve lymph nodes (No. 106recL) and the right cervical paraesophageal lymph nodes (No. 101R) were observed on the medial side of the visceral sheath, with the RLN. CONCLUSION: The recurrent nerve, which branched off from the vagus nerve descending along the vascular sheath, ascended the medial side of the visceral sheath after inversion. However, no clear visceral sheath could be identified in the inverted area. Therefore, during radical esophagectomy, the visceral sheath along No. 101R or 106recL may be recognized and available.

Histological study of the thin membranous dense connective tissue around the middle and lower thoracic esophagus, caudal to the bifurcation of the trachea.

OBJECTIVE: We previously reported on the thin membranous dense connective tissue around the esophagus in the upper mediastinum. This time, we histologically investigated the existence of similar structures in the middle and lower mediastinum, caudal to the bifurcation of the trachea. METHODS: Semi-sequential transverse sections of the mediastinum were obtained from two cadavers. Hematoxylin and eosin staining and Elastica van Gieson staining were performed. RESULTS: In the middle mediastinum, the "visceral sheath" could not be observed completely around the esophagus. In the lower mediastinum, the thin membranous dense connective tissue was observed beneath the pericardium on the ventral side of the esophagus. On the dorsal side of the esophagus, two thin membranous dense connective tissues were similarly observed in two cadavers. One existed between the dorsal side of the esophagus and the three vessels (i.e., the descending aorta, the azygos vein and the thoracic duct) and was integrated with the thin membranous dense connective tissue of the ventral side of the esophagus at the bilateral side of the esophagus. This integrated dense connective tissue reached the left subpleural region and the adventitia of the aorta on the left side and the peripleural and pulmonary hilum on the right side. The other thin membranous dense connective tissue, which represents the "vascular sheath", was observed between the descending aorta and the thoracic duct. CONCLUSION: These two thin membranous dense connective tissues, which are considered to represent the visceral sheath and vascular sheath, are thought to be available as optimal dissecting layers for radical esophagectomy.

Aortic inflation with agar injection is a useful method of cadaveric preparation which creates a mediastinal anatomy that better mimics the living body for surgical training.

In cadavers, even Thiel-embalmed cadavers, the arteries (especially the thoracic aorta) are extremely collapsed. This is in marked contrast to the state of the arteries in a living body. Aortic inflation is necessary to improve this unfavorable situation for anatomical observation or dissection. To inflate the aorta, we injected 500 ml of hot liquid agar into the aorta using a 18-Fr catheter inserted into the common femoral artery and subclavian artery. The injected agar then rapidly cools to room temperature and solidifies. As a result, the thoracic aorta remains sufficiently and constantly inflated in the mediastinum. This method is not only easy and inexpensive, but also useful and effective for achieving a life-like anatomy in cadavers used in surgical training for operations involving mediastinal organs, with the exception of the heart and great vessels.

The usefulness of a bilateral trans-cervical pneumomediastinal approach for mediastinoscopic radical esophagectomy: a right transcervical approach is an available option.

OBJECTIVE: We investigated the merits and demerits of right cervical open surgery with right trans-cervical pneumomediastinal approach in mediastinoscopic esophagectomy. METHODS: Ten thoracic esophageal cancer patients were treated using this approach. Under pneumomediastinum via a right neck incision, the right cervical and upper mediastinal paraesophageal lymph nodes were dissected. The left recurrent nerve lymph nodes were dissected using a left trans-cervical pneumomediastinal approach. The subaortic arch to the left tracheobronchial lymph nodes was dissected with a combined right and left trans-cervical crossover approach. RESULTS: The average number of dissected lymph nodes among the right cervical and upper mediastinal paraesophageal lymph nodes identified with a right cervical open/right trans-cervical mediastinoscopic/right thoracoscopic approach was 3.2/4.0/0.6, respectively. The average number of dissected lymph nodes among the subaortic arch to the left tracheobronchial lymph nodes with a right trans-cervical mediastinoscopic/right thoracoscopic approach was 1.5/0.6, respectively. These findings indicate that, without using the right trans-cervical pneumomediastinal approach, it might be impossible to successfully remove some of the right cervical and upper mediastinal paraesophageal lymph nodes and the subaortic arch to the left tracheobronchial lymph nodes lymph nodes. Regarding surgical complications, one case of bilateral recurrent nerve palsy as well as two cases on the right and two cases on the left were noted. CONCLUSIONS: Although the rate of recurrent nerve palsy should still be reduced, a bilateral (especially right-sided) trans-cervical pneumomediastinal approach is an available option for achieving sufficient upper mediastinal lymph node dissection and esophagectomy.

A feasibility study of mediastinoscopic radical esophagectomy for thoracic esophageal cancer from the viewpoint of the dissected mediastinal lymph nodes validated with thoracoscopic procedure: a prospective clinical trial.

PURPOSE: A prospective trial evaluated the feasibility and safety of "mediastinoscopic esophagectomy with lymph node dissection" (MELD). METHODS: Eligible patients had thoracic esophageal squamous cell carcinoma, excluding T4, a bulky primary lesion or distant metastasis. Ten patients were enrolled and treated between September 2015 and March 2018. Additionally, to verify the integrity of the mediastinal lymph node dissection, thoracoscopic observation and lymph node dissection were followed. The primary end point was the integrity of mediastinal lymph node dissection. The secondary end points were the short-term outcomes, including mortality and morbidity. RESULTS: The median number of dissected lymph nodes in the upper mediastinal to cervical region and middle to lower mediastinal region by mediastinoscopy/thoracoscopy was 27/0.5 and 11.5/0, respectively. The median total operation time was 615 min, the median bleeding amount was 476 ml, and the median postoperative hospital stay was 15.5 days. Regarding complications of more than grade III according to the Clavien-Dindo classification, four had sputum excretion difficulty, one had pneumothorax and one had bilateral recurrent nerve palsy, but none required conversion to thoracotomy, and no operative deaths occurred. CONCLUSION: Although the rate of recurrent nerve palsy still should be reduced, our mediastinoscopic lymphadenectomy technique is closely similar to radical esophagectomy.

Histological study of the thin membranous structure made of dense connective tissue around the esophagus in the upper mediastinum.

BACKGROUND: The structure of the fascia in upper mediastinum has already been reported from gross anatomical viewpoints by Sarrazin. But it is necessary to understand meticulous anatomy for thoracoscopic or mediastinoscopic surgery. So herein, we investigate histologically the thin membranous structure made of dense connective tissues. METHODS: Semi-sequential transverse sections of the mediastinum were obtained from three cadavers. Hematoxylin and eosin staining, Elastica van Gieson staining, and Masson trichrome staining were performed to identify the presence and location of the thin membranous structure made of dense connective tissues. RESULTS: The "visceral sheath" and "vascular sheath," as previously described by Sarrazin, were observed histologically. These two thin membranous structures do not surround the esophagus and trachea cylindrically. In addition, the "visceral sheath" on the right side of the upper mediastinum was unclear in comparison to the left side. The "visceral sheath" (on the left side) gradually became unclear, and seemed to almost disappear; the esophagus was found to be very close to the thoracic duct on the caudal side of the bifurcation of the trachea. Although the left recurrent nerve was located inside the "visceral sheath" in all cadavers, the left recurrent nerve lymph nodes were located inside the "visceral sheath" in cadaver 1 and between the "visceral sheath" and "vascular sheath" in cadaver 3. CONCLUSION: The "visceral sheath" around the esophagus in the upper mediastinum was histologically demonstrated; however, the findings were not constant.

Anatomical study of the left superior mediastinal lymphatics for tracheal branches of left recurrent laryngeal nerve-preserving mediastinoscope-assisted surgery in esophageal cancer.

PURPOSE: Curative treatment of esophageal cancer requires meticulous superior mediastinal lymphadenectomy, in addition to esophagectomy, because superior mediastinal lymph node metastases are common in esophageal cancer. When preserving the tracheal branches of the left recurrent laryngeal nerve (RLN), good anatomical understanding is required for confirmation of the positional relationships between the courses of lymphatic vessels, lymph node distribution, and the left RLN and its tracheal branches. We performed a detailed anatomical examination of these relationships. METHODS: Macroscopic anatomical observation and histological examination was performed on cadavers. In addition to hematoxylin and eosin staining, immunostaining using antipodoplanin antibody D2-40 (podoplanin) was performed to identify the lymphatic vessels. RESULTS: The tracheal branches of the left RLN were clearly observed, but no lymphatic vessels crossing the ventral or dorsal side of the branches were identified either macro-anatomically or histologically. CONCLUSION: No complex lymphatic network structure straddling the plane composed of tracheal branches of the left RLN was found in the left superior mediastinum. This suggests that dissection of the lymph nodes around the left RLN via the pneumomediastinum method using the left cervical approach may allow preservation of the tracheal branches of the left RLN by maintaining dissection accuracy.

A prospective study of nutritional supplementation for preventing oral mucositis in cancer patients receiving chemotherapy.

BACKGROUND AND OBJECTIVES: Patients undergoing chemotherapy often develop distressing adverse effects such as oral mucositis and diarrhea. Nutritional support with elemental diet is effective against various gastrointestinal complications and may exert protective effects against adverse effects induced by chemotherapy. To evaluate the influence of elemental diet on chemotherapy-induced oral mucositis and diarrhea, we conducted a randomized control trial in patients with esophageal cancer undergoing chemotherapy. METHODS AND STUDY DESIGN: Twenty esophageal cancer patients receiving chemotherapy with 5-fluorouracil plus cisplatin were assigned randomly to one of the following two groups: (1) receiving elemental diet with Elental (one pack per day) for 14 days and (2) not receiving Elental during chemotherapy. The severity of oral mucositis and diarrhea was graded using clinical examination by doctors and a standard questionnaireon days 1-14. RESULTS: Based on the analysis of the standard questionnaire, the distribution of the maximum severity of oral mucositis showed a statistically significant reduction in the Elental group (p=0.020), while clinical examination showed insignificant reduction but shift toward lower grade. In the Elental group, the incidence of oral mucositis (grade >=2) reduced consistently and the median grade was lower at all-time points. Regarding diarrhea, no difference was observed between the two groups based on the analysis of the standard questionnaire and clinical examination results. CONCLUSIONS: This study illustrates the effectiveness of oral elemental diet in preventing oral mucositis during chemotherapy. This is a preliminary report and further study with larger patients groups should be devoted to optimization of efficacy.

Endoscopic assessment 1 day after esophagectomy for predicting cervical esophagogastric anastomosis-relating complications.

BACKGROUND: There are no useful methods for predicting anastomosis-relating complications after esophagectomy; however, anastomotic leakage remains one of the most serious postoperative complications. We retrospectively investigated the appropriateness of endoscopic examinations on postoperative day 1 (POD 1) for assessing esophageal reconstruction by analyzing the endoscopic findings 1 day after the operation and evaluating the healing process at the site of anastomosis in patients treated with esophageal reconstruction. METHODS: Between 2010 and 2013, we performed esophageal reconstructive surgery using a retrosternal gastric graft and cervical anastomosis and conducted endoscopic examinations to assess the esophagogastric anastomosis on POD 1 in 153 patients. On endoscopy performed on POD 1, we identified mucosal color change (MCC) in the proximal gastric graft as an important finding that may be indicative of local circulatory failure in gastric grafts. One week after the operation, endoscopic examinations subsequently showed significant mucosal defects around the site of anastomosis that were expected to result in anastomotic leakage as a marker of poor healing of anastomosis as well as leakage. RESULTS: We identified the findings of MCC in 36 patients evaluated with endoscopic examinations performed on POD 1. Furthermore, the endoscopic examinations performed 1 week after the operation revealed poor healing of the anastomosis site in 23 patients, including one patient with major anastomotic leakage. Therefore, poor healing of the anastomosis site more frequently occurred in 20 of the 36 patients (55.6%) who exhibited MCC on the endoscopic examinations performed on POD 1 than in three of the 117 patients (2.6%) who had normal endoscopic findings on POD 1 (p < 0.001). CONCLUSIONS: Early endoscopy performed on POD 1 helps to predict the development of poor healing of esophagogastric anastomosis around 1 week after the operation by identifying the findings of MCC in the proximal gastric graft.

Relationships between Micro-Vascular and Iodine-Staining Patterns in the Vicinity of the Tumor Front of Superficial Esophageal Squamous Carcinoma.

OBJECTIVE: The aim of the present study was to clarify differences between micro-vascular and iodine-staining patterns in the vicinity of the tumor fronts of superficial esophageal squamous cell carcinomas (ESCCs). METHODS: Ten consecutive patients with ESCCs who were treated by endoscopic submucosal dissection (ESD) were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in total using image-enhanced magnifying endoscopy. We classified the micro-vascular and iodine-staining patterns into three types: Type A, in which the line of vascular change matched the border of the iodine-unstained area; Type B, in which the border of the iodine-unstained area extended beyond the line of vascular change; Type C, in which the line of vascular change extended beyond the border of the iodine-unstained area. Then, by examining histopathological sections, we compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous areas and normal squamous epithelium. RESULTS: We investigated 160 sites that the adequate quality of pictures were obtained. There was no case in which the line of vascular change completely matched the whole circumference of the border of an iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological examination showed that the mean diameter of the IPCLs in normal squamous epithelium was 16.2±3.7 µm, whereas that of IPCLs in cancerous lesions was 21.0±4.4 µm. CONCLUSIONS: The development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium.

Mediastinoscopic subaortic and tracheobronchial lymph node dissection with a new cervico-hiatal crossover approach in thiel-embalmed cadavers.

The use of mediastinal surgery for minimally invasive esophagectomy (MIE) has been proposed; however, this method is not performed as radical surgery because it has been thought to be impossible to perform complete upper mediastinal dissection, including the left tracheobronchial lymph nodes (106tbL). We herein describe a new method for performing complete dissection of the upper mediastinum. We developed a method for performing complete mediastinoscopic esophagectomy as radical surgery via the bilateral transcervical and transhiatal approach in 6 Thiel-embalmed human cadavers. The lower and middle mediastinal lymph nodes are dissected via the transhiatal approach. The dorsal side of the left recurrent nerve is dissected up to the aortic arch and left recurrent nerve lymph nodes (106recL) are dissected under pneumomediastinum. Next, the right recurrent nerve lymph nodes (106recR) are dissected. The cartilage of the left main bronchus is dissected and pushed downward, thereby obtaining a good view between the aortic arch and left main bronchus via the transhiatal approach. The 106tbL lymph nodes are dissected until the aortic arch is reached. Simultaneously, the lymph nodes are dissected via a right cervical incision. This method is termed the "cross-over technique." We herein demonstrated that the upper mediastinal lymph nodes, including the 106tbL nodes, can be dissected using the bilateral transcervical and transhiatal approach under pneumomediastinum and named this method "mediastinoscopic esophagectomy with lymph node dissection" (MELD). MELD is therefore considered to be a useful modality based on our experience with Thiel-embalmed human cadavers.

[A Case of Drug-Induced Thrombocytopenia Resulting from Sensitivity to Oxaliplatin].

A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature.

Copper-deficiency anemia after esophagectomy: A pitfall of postoperative enteral nutrition through jejunostomy.

INTRODUCTION: Copper deficiency leads to functional disorders of hematopoiesis and neurological system. There have been some reports of copper deficiency occurring to the patients on enteral nutrition through a jejunostomy in long-term-care hospitals. However, it is extremely rare to find patients with copper deficiency several months after esophagectomy, regardless of enteral nutrition through the jejunostomy. To the best of our knowledge, this is the first case report of a patient who experienced copper-deficiency anemia after esophagectomy and subsequent enteral nutrition through the jejunostomy. PRESENTATION OF CASE: A 73-year-old man presented with pulmonary failure after esophagectomy for esophageal cancer with video-assisted thoracoscopic surgery, and needed long-term artificial ventilator support. Nutritional management included enteral nutrition through a jejunostomy from the early postoperative period. Copper-deficiency anemia was detected 3 months postoperatively; therefore, copper supplementation with cocoa powder was performed, and both serum copper and hemoglobin levels subsequently recovered. DISCUSSION: Copper-deficiency anemia has already been reported to occur in patients receiving enteral nutrition in long-term care hospitals. However, this is the first case report of copper deficiency after esophagectomy despite administration of standard enteral nutrition through the jejunostomy for several months. CONCLUSION: It is extremely rare to find copper-deficiency anemia several months after esophagectomy followed by enteral nutrition through the jejunostomy. However, if anemia of unknown origin occurs in such patients, copper-deficiency anemia must be considered among the differential diagnoses.

Vocal cord assessment with transnasal endoscopy in intubated patients after esophagectomy.

BACKGROUND: Vocal cord paralysis (VCP) is one of the postoperative complications after radical esophagectomy. VCP may also lead to serious morbidities such as respiratory distress and aspiration pneumonia. Therefore, an early diagnosis of VCP is meaningful in the postoperative management of patients undergoing esophagectomy. We evaluated a new practical method for diagnosing postoperative VCP. METHODS: The laryngeal assessment of 30 patients was performed, and the presence of VCP was inferred while the following 15 patients by endoscopy before extubation after performing consecutive radical esophagectomy in 45 esophageal cancer patients. The vocal cord mobility, including adduction and abduction, were assessed by inserting the tip of a transnasal endoscope near the vocal cord in the awake patients with orotracheal intubation on the first postoperative day. The presence of VCP was reevaluated after extubation. RESULTS: Eleven of the 30 patients assessed after radical esophagectomy had unilateral VCP and one patient had bilateral VCP. The abduction findings were useful for assessing VCP and the sensitivity, specificity, positive and negative predictive values and accuracy were 97.9%, 100%, 100%, 92.9% and 98.3%, respectively. The results of the following 15 patients were closely similar. CONCLUSIONS: The VCP during orotracheal intubation is assessable by transnasal endoscopy.

Changes in the microvascular structure of mucosal squamous cell carcinoma of the esophagus and their significance in tumor progression.

BACKGROUND: To identify the clinical T stage by endoscopy is a major diagnostic goal for superficial esophageal squamous cell carcinoma (ESCC). The completion of a microvascular morphological study of mucosal lesions is necessary to optimize therapy. MATERIALS AND METHODS: Images of 197 intra-papillary capillary loops (IPCLs) captured by magnified endoscopy from 15 esophagectomy specimens were studied for their morphological features and IPCL dimensions. RESULTS: The microvascular morphology was classified into four basic major patterns: 1. spiral loop, 2. wide loop (WL), 3. globular (G) and 4. reticular pattern. The microvascular features and dimensions differed according to the depth of tumor invasion. Especially the mean bundle outline (IPCL diameter) showed significant changes as 20.02, 22.32, and 27.08 µm, respectively, for M1, M2 and M3, respectively (M1:M2 P < 0.05, M2:M3 P < 0.01). CONCLUSIONS: During tumor stage progression, a high-volume blood demand and cancer cell overgrowth to occupy the laminar propria mucosa (LPM) cause obvious elongation, thickening, branching, irregularity and deformity of the IPCL, which were characteristics of M3 lesions. The results of the present study support and can be applied with the current Japanese classification for improving the diagnostic accuracy, especially to differentiate between M2 and M3 lesions based on the endoscopic findings.

Internal pressure of the conduit during endoscopy on the day after esophagectomy.

BACKGROUND: In gastrointestinal surgery, anastomosis can result in various complications. Anastomosis is evaluated using classical examinations. The most reliable one is endoscopy, which provides direct information on the anastomosis and conduit. But the influence of endoscopy on anastomosis is uncertain. METHODS: The internal pressure of a graft during endoscopy was measured in 36 patients who received esophagectomy, by utilizing the decompression tube which was inserted into the graft during operation. We filled the tube with water and measured the maximum water level in a centimeter water column. All examinations were routinely performed on the day after operation, and thin endoscopes were selected for reducing the stress. RESULTS: The internal pressure before endoscopy ranged from 6 to 20 cm H2O, and during endoscopy ranged from 9 to 27 cm H2O. The difference in the internal conduit pressure in each patient ranged from 1 to 9 cm H2O. There was no increase in complications caused by endoscopy, including anastomotic leakage. CONCLUSION: This study is the first to report changes in internal pressure due to the endoscope by direct measurement. The pressure gradient observed was below the physiological pressure during swallowing. These results suggest that endoscopy is a safe examination even after surgery.

Esophageal squamous cell carcinoma developed 11 years after allogeneic bone marrow transplantation for acute lymphatic leukemia.

Younger patients (aged <30 years) presenting with esophageal cancer are rare. Bone marrow transplantation offers a curative therapy in patients with malignant and nonmalignant lymphohematopoietic diseases and other disorders. However, one important late complication in transplantation survivors is the development of secondary malignancies including solid tumors. Although some solid cancers have been demonstrated to occur after bone marrow transplantation, only a few cases of esophageal squamous cell carcinoma have thus far been reported. We herein describe the case of a 27-year-old male with esophageal squamous cell carcinoma, who was diagnosed with T-cell-type acute lymphatic leukemia at the age of 12 and relapsed 5 years later. He achieved a second complete remission and underwent bone marrow transplantation at the age of 17. A genetic analysis revealed germ-line lineage-derived chimeric cellular populations of the donor and patient on both the esophageal squamous cell carcinoma and non tumorous portions of the patient's esophageal mucosa with a preponderance of the patient's germ-line lineage-derived cells, suggesting that repopulated donor-derived hemopoietic stem cells in the esophageal epithelia only partially contributed to the carcinogenesis of esophageal squamous cell carcinoma several years after bone marrow transplantation. Multiple events occurring during the course of treatment for primary hematological disorder may play an important role in the development of esophageal squamous cell carcinoma.

A pilot trial of S-1 plus irinotecan chemotherapy for esophageal adenocarcinoma.

BACKGROUND/AIMS: This study investigated the clinical efficacy and toxicity of the combination chemotherapy using S-1 plus irinotecan for esophageal adenocarcinoma. METHODOLOGY: This study included 10 patients with histologically confirmed adenocarcinoma of the esophagus or esophagogastric junction between April 2005 and August 2011. S-1 was administered orally at a dose of 80 mg/m²/day from day 1 to 14 and irinotecan was given intravenously on day 1 and 8 at a dose of 80 mg/m². RESULTS: A total of 65 cycles were administered and the response rate was 62.5%. The 50% progression-free survival period and the 50% overall survival period for all of the patients was 8.4 months and 19.1 months, respectively and 5.9 months and 16.3 months for the 8 patients with unresectable or recurrent tumors, respectively. The 2 patients that received adjuvant chemotherapy demonstrated a prophylactic effect for the post-operative recurrence. On the other hand, this therapy showed no severe non-hematological toxicity and only 20% experienced grade 3 neutropenia. As a result, the treatment regimen could generally be performed in an outpatient basis. CONCLUSIONS: The combination chemotherapy using S-1 and irinotecan showed tolerable clinical efficacy in terms of the response rate, survival and toxicity for esophageal adenocarcinoma.