Satoru Matono

Optimal Lymphadenectomy for Squamous Cell Carcinoma in the Thoracic Esophagus: Comparing the Short- and Long-term Outcome among the Four Types of Lymphadenectomy

Controversy continues over the optimal extent of lymphadenectomy (regional versus three-field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three-field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three-field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three-field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three-field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long-term survival, whereas there was not a large difference in short-term and long-term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer.

Esophagectomy: Is It Necessary after Chemoradiotherapy for a Locally Advanced T4 Esophageal Cancer? Prospective Nonrandomized Trial Comparing Chemoradiotherapy with Surgery versus without Surgery

The need for surgery after chemoradiotherapy for a T4N0-1M0 squamous cell carcinoma in the thoracic esophagus was evaluated. A series of 53 patients were enrolled in this prospective nonrandomized trial from among 124 patients with an esophageal cancer assessed as T4 in Kurume University Hospital from 1994 to 2002. After the first chemoradiotherapy cycle, which consisted of radiotherapy in a total dosage of 36 Gy and chemotherapy using cisplatin (CDDP) and 5-fluorouracil (5FU), the patients each decided, after being informed of the efficacy of the chemoradiotherapy, whether to undergo surgery. All patients, including those who had undergone surgery and those who had not, later underwent a second chemoradiotherapy cycle consisting of radiotherapy in a total dosage of 24 Gy and chemotherapy using CDDP and 5FU, as far as practicable. Among the responders to the first chemoradiotherapy cycle, there was no significant difference in the long-term (5-year) survival rate between the 18 patients who underwent esophageal surgery and the 13 patients who did not (23% vs. 23%). Among the nonresponders, the 11 patients who underwent surgery showed a tendency toward longer survival than the five patients who had had no surgery. The nonresponders had 1- and 2-year survival rates of 64% and 33%, respectively. The corresponding rates for the 5 nonsurgical patients who completed the two chemoradiotherapy cycle were 20% ands 20%, respectively. For a T4N0-1M0 squamous cell carcinoma in the thoracic esophagus, full-dosage chemoradiotherapy (definitive chemoradiotherapy) is preferred for responders to a half-dose of chemoradiotherapy as much as esophagectomy, whereas esophagectomy may be preferred for nonresponders.

Photodynamic therapy for large superficial squamous cell carcinoma of the esophagus

BACKGROUND Photodynamic therapy (PDT) has been found to be safe and effective in patients with small early esophageal squamous cell carcinoma (SCC). However, its efficacy for widespread superficial SCC has not yet been confirmed. OBJECTIVE To assess the long-term survival, complications, and recurrence of PDT for large superficial esophageal SCC. DESIGN Retrospective study. SETTING Tertiary referral center. PATIENTS A total of 38 patients with superficial SCC of the esophagus. All patients had a large unifocal lesion or multifocal lesions that were too large to be resected endoscopically. In addition, all patients were physiologically unfit for esophagectomy or had refused surgery. INTERVENTIONS PDT with porfimer sodium. MAIN OUTCOME MEASUREMENTS Clinical follow-up, long-term survival, complications, and recurrence were evaluated. RESULTS Thirty-one patients (82%) had mucosal cancer (T1m), and 7 (18%) had submucosal cancer (T1sm). No patient had lymph node involvement. Nineteen patients had other primary malignancies. Complete remission was achieved in 33 (87%). At the time of writing, 28 patients (74%) were alive without recurrence. After a median follow-up period of 64 months (range, 7-125 months) after PDT, the overall 5-year survival rate was 76%. There was no treatment-related mortality. LIMITATIONS Retrospective study with a small number of patients. CONCLUSIONS This long-term follow-up study revealed that PDT was a potentially curative treatment for large superficial esophageal SCC. PDT might be a reasonable alternative to esophagectomy or to endoscopic resection for patients with superficial SCC of the esophagus without lymph node metastasis.

Surgical management for small cell carcinoma of the esophagus

Esophageal small cell carcinoma (SmCC) has been regarded as a rare and aggressive tumor with early metastasis. The optimal treatment has not yet been established, and the role of surgery has remained controversial. In this retrospective study, we report seven cases studies of SmCC of the esophagus and analyze the clinical outcomes after surgery. Between 1986 and 2007, there were seven patients with esophageal SmCC treated surgically in our institution. All the patients with clinically limited disease underwent transthoracic esophagectomy with lymphadenectomy. Lymph node involvement was found in all cases irrespective of the depth of tumor invasion. Three of the seven patients were diagnosed as having an extensive disease on pathological examination after esophagectomy. Five patients received postoperative chemotherapy. Two patients are alive with no recurrence at 16 months and at 45 months after surgery. Another one without chemotherapy survived 93 months and died of another disease. The remaining four patients died of recurrent disease or another disease. The median overall survival to date of these patients was 16 months (range 12-93 months). Esophagectomy with lymphadenectomy resulted in a relatively better survival in some patients with esophageal SmCC. We concluded that surgery may be helpful as part of multimodality treatment in selected patients with esophageal SmCC.

Adjuvant Chemotherapy after Radical Resection of Squamous Cell Carcinoma in the Thoracic Esophagus: Who Benefits?

Background: A definitive combined modality therapy superior to surgery alone has not yet been found for esophageal cancer. This retrospective study investigated the impact of postoperative adjuvant chemotherapy in patients who underwent curative (R0) esophagectomy with radical lymphadenectomy. Study Design: Two hundred and eleven patients with a squamous cell carcinoma in the thoracic esophagus who underwent transthoracic curative (R0) esophagectomy with radical lymphadenectomy, such as 3-field lymphadenectomy or total 2-field lymphadenectomy, between 1988 and 2000, were retrospectively reviewed. Ninety-four patients received postoperative chemotherapy – 2 courses of cisplatin (CDDP) plus fluorouracil (5-FU) or vindesine (VDS) – while the other 117 patients received surgery alone. The overall survival rate was compared between the two groups after being stratified by the numbers of the metastasis- positive lymph nodes. Results: Only in the subgroup of patients with 8 or more lymph nodes metastasis- positive, the surgery-with-postoperative-chemotherapy group had a significantly better survival than the surgery-alone group. No significant difference was found in survival between the two groups in any other stratified subgroup. Conclusions: Postoperative adjuvant chemotherapy following curative (R0) esophagectomy with radical lymphadenectomy such as 3-field lymphadenectomy or total 2-field lymphadenectomy provided a benefit only in patients having metastasis in a large number – 8 or more – lymph nodes.

Locoregional adoptive immunotherapy resulted in regression in distant metastases of a recurrent esophageal cancer

Abstract. Esophageal cancer is one of the most common malignant diseases. However, postoperative recurrences are still resistant to currently available radiochemotherapy. We recently reported a study on the initial clinical efficacy of locoregional adoptive immunotherapy for advanced esophageal cancer. We report here our clinical experience of remarked responses in distant metastatic lesions in a patient with recurrent cancer after receiving this immunotherapy. A male patient underwent curative surgery, and presented with multiple recurrent metastases in the supraclavicular lymph nodes (LNs), liver, and abdominal aortic LNs. Autologous tumor-activated lymphocytes (AuTLs) generated ex vivo were regionally injected into supraclavicular LNs every 2 weeks 13 times. Mean numbers of the administrated cells were 0.8 × 109 cells/injection. AuTLs established from peripheral blood lymphocytes stimulated by autologous tumor cells with interleukin-2 were tested for their cytotoxicity before every treatment. During immunotherapy, Grade 2 diarrhea and fever were observed. The clinical partial responses were obtained in all lesions and were sustained for 11 months. Because clinical toxicity was tolerable, this immunotherapy might be useful for patients with far-advanced esophageal cancers.

Outcomes of multimodality therapy for stage IVB esophageal cancer with distant organ metastasis (M1-Org)

Esophageal cancer patients with distant organ metastasis have usually been treated only to palliate symptoms without multimodality therapy. The current study evaluates the role of multimodality therapy in esophageal squamous cell cancer patients with distant organ metastasis. Between February 1988 and January 2007, 80 esophageal squamous cell cancer patients with distant organ metastases were treated at our institution. Multimodality therapy was performed in 58 patients: 43 patients received chemoradiotherapy, 13 underwent surgery followed by chemotherapy and/or radiation therapy, and two received chemotherapy or chemoradiotherapy followed by surgery. Thirteen patients received single-modality therapy; chemotherapy, radiotherapy, or surgery alone. The remaining nine patients received best supportive care alone. The metastatic organ was the liver (n= 40), the lungs (n= 33), bone (n= 10), and other (n= 6). Nine patients had metastasis in two organs. There was no difference in the median survival among the sites of organ metastasis, lung, liver, or bone (P= 0.8786). The survival of patients treated with multimodality therapy was significantly better than that of the patients who received single-modality therapy or best supportive care alone (P < 0.0001). In patients treated with multimodallity therapy, there was no difference in survival for patients treated with surgery compared with patients treated without surgery (P= 0.1291). This retrospective study involves an inevitable issue of patient selection bias. However, these results suggested that multimodality therapy could improve survival of the esophageal squamous cell cancer patients with distant organ metastasis.

Thoracic endovascular aortic repair for aortic complications after esophagectomy for cancer: report of three cases.

Aortic complications after esophageal cancer surgery are rare and usually fatal. Here, we report three patients who underwent thoracic endovascular aortic repair (TEVAR) for aortic complications after esophagectomy for cancer. In the first case, aortic rupture was caused by pyothorax due to residual tumor after esophagectomy. In the second case, aortic rupture was caused by pyothorax due to anastomotic leakage. In the third case, a pseudoaneurysm was caused by surgical injury during esophagectomy. TEVAR was safe and effective for severe aortic complications when graft infection was avoided. The first case died of sepsis on the 84th postoperative day, and the other two cases have survived 4 years and 2 years to date.

Reflux esophagitis and columnar-lined esophagus after cervical esophagogastrostomy (following esophagectomy)

Reflux esophagitis (RE) and columnar-lined esophagus (CLE) are frequently observed after esophagectomy. The incidence of these conditions according to time and to the route of esophageal reconstruction after esophagectomy remains unknown. The aim of this study was to clarify any changes and differences of the incidence of RE and CLE in patients who underwent gastric tube reconstruction after esophagectomy. A hundred patients who underwent cervical esophagogastrostomy after resection of the thoracic esophagus were included in this study. We reviewed their endoscopic findings at 1 month, at 1 year and at 2 years after surgery, and compared the incidence rates of RE and CLE with the passage of time and among the three reconstruction routes; a subcutaneous route, a retrosternal route, and a posterior mediastinal route. The incidence rate of RE was 42%, 37% and 38%, at 1 month, 1 year and at 2 years after surgery, respectively. There was no significant difference in the incidence of RE according to the time after surgery. The incidence rate of severe RE (Grade C and D in the Los Angeles Classification) was 9% percent at 1 month after surgery, 18% at 1 year after surgery and 22% at 2 years after surgery, significantly increasing with passage of time. The incidence rate of CLE was 0% at 1 month after surgery, 14% at 1 year after surgery and 40% at 2 years after surgery, significantly increasing with passage of time. No difference was observed in the incidence of RE and that of CLE among the three routes of esophageal reconstruction. Severe RE and CLE increase with passage of time after cervical esophagogastrostomy. Therefore, careful endoscopic follow-up is necessary for such patients irrespective of the route of esophageal reconstruction.

Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma

BackgroundRecently, several immune checkpoint inhibitors have been developed and are being used to treat malignant melanoma, lung cancer, and other cancers. Several reports have indicated that tumor-infiltrating lymphocytes (TILs) are associated with clinical and histopathologic risk factors in various cancers. However, the role of TILs in esophageal squamous cell carcinoma (ESCC) has not been well studied. This study aimed to investigate the perilesional status of TILs in ESCC and to show associations between TILs and clinical variables.MethodsThe study enrolled 277 ESCC patients. Evaluation of TILs was performed according to the criteria of the International TILs Working Group 2014, and associations between TIL and clinicopathologic variables were examined.ResultsMost of the clinicopathologic factors were not statistically associated with TIL status. The number of patients who received adjuvant therapy was significantly larger in the TIL-negative group. Cancer-specific survival (CSS) of patients in the TIL-positive group was significantly better than in the TIL-negative group. Among the patients who received adjuvant therapy, CSS was significantly better in the TIL-positive group than in the TIL-negative group. Uni- and multivariate analyses identified tumor depth and TIL status as independent prognostic factors for CSS. Among the other clinicopathologic variables, TIL status was the strongest CSS indicator.ConclusionTumor-infiltrating lymphocyte status is a strong predictor of good prognosis for ESCC patients.