Susumu Sueyoshi

Optimum Treatment Strategy for Superficial Esophageal Cancer: Endoscopic Mucosal Resection versus Radical Esophagectomy

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.

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.

Impact on Outcome of Additional Microvascular Anastomosis—Supercharge—on Colon Interposition for Esophageal Replacement: Comparative and Multivariate Analysis

Abstract. The impact on the outcome of an additional microvascular anastomosis—supercharge—on colon interposition for esophageal replacement was retrospectively evaluated by comparing it with colon interposition without supercharge. A series of 53 patients had undergone colon interposition for esophageal replacement at Kurume University Hospital from 1981 to 1996. The postoperative courses and the morbidity and mortality rates were compared between the 24 patients who underwent colon interposition without supercharge from 1981 to 1988 and the other 29 patients who underwent colon interposition with supercharge from 1989 to 1996. Risk factors for leakage of the esophagocolostomy and for hospital mortality after colon interposition were evaluated by multivariate analysis. Colon interposition with supercharge required a longer operation time but resulted in a lower incidence of necrosis in the colon graft and leakage in the esophagocolostomy (Odds ratio = 34), a shorter duration until peroral intake, and a shorter hospital stay compared to colonic interposition without supercharge. The addition of supercharge to colon interposition for esophageal replacement has been an effective option that has prevented serious complications caused by graft ischemia.

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.

Expression of vascular endothelial growth factor as a prognostic factor in node-positive squamous cell carcinoma in the thoracic esophagus: Long-term follow-up study

To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) in squamous cell carcinoma in the thoracic esophagus, particularly as a prognostic factor, we have investigated the correlation between VEGF expression in tumor cells and microvessel density (MVD), pathologic factors, and survival. A total of 92 specimens, each from a thoracic esophageal squamous cell cancer patient who underwent transthoracic curative R0 esophagectomy between 1991 and 1994, were examined immunohistochemically using anti-human VEGF and anti-human von Willebrand factor antibodies. The incidence of VEGF expression in the tumor cells was relatively low, at 23.9% of all specimens. There was no significant correlation between VEGF expression and histopathologic factors. The MVD at the tumor margin in patients with VEGF-positive tumor cells was significantly greater than that in VEGF-negative cases (35.2 ± 8.9 vs. 22.7 ± 8.2). The survival rate for patients with VEGF expression was significantly lower than that of those without VEGF expression; the same situation was found in node-positive patients but not in node-negative patients. In addition, multivariate analysis revealed that VEGF expression was an independent prognostic factor in node-positive patients. VEGF may be implicated in the definition of the malignant phenotype of squamous cell esophageal cancer via tumor angiogenesis. Accordingly, VEGF expression in the tumor cells could be a useful prognostic factor for esophageal cancer, particularly in node-positive patients.

Second-Line Combination Chemotherapy with Docetaxel for Cisplatin-Pretreated Refractory Metastatic Esophageal Cancer: A Preliminary Report of Initial Experience

Background and Aims: Patients with esophageal cancer often develop metastatic disease after esophageal resection and generally receive cisplatin-based chemotherapy or chemoradiotherapy. The efficacy and toxicity of the combination of docetaxel, 5-fluorouracil (5-FU) and cisplatin (DFC) as a second-line chemotherapy were evaluated in patients with postoperative metastatic esophageal cancer refractory to cisplatin-based chemotherapy. Patients and Methods: Twenty patients with metastatic esophageal cancer after esophagectomy refractory to cispatin-based therapy were included in this study. The DFC regimen consisted of docetaxel (60 mg/m2) on day 1, 5-FU (500 mg/day) on days 1–5 and cisplatin (10 mg/day) on days 1–5, being repeated every 3 weeks. Results: A total of 49 cycles (median 2, range 1–6) was administered to 20 patients. The median follow-up was 8 months (range 3–24). Of the 20 patients, 1 had a complete response, 6 had a partial response, 6 had stable and 7 had progressive disease. Median time to progression for all patients was 4 months (95% Cl 1.7–5.6). The median overall survival for all patients was 8 months (95% CI 5.7–10.3). The major toxicity was myelosuppression. Neutropenia of grade 3 or more occurred in 13 patients (65%), and thrombocytopenia of grade 3 occurred in 1 patient (5%). Febrile neuropenia was observed in 1 patient (5%). There was no treatment-related mortality. Conclusion: DFC is a feasible and promising regimen as a second-line therapy in metastatic/recurrent esophageal cancer refractory to cisplatin-based chemotherapy.

Gastropericardial and gastrobrachiocephalic vein fistulae caused by penetrating ulcers in a gastric pedicle following esophageal cancer resection: A case report

The gastric pedicle is commonly used for reconstruction following resection of esophageal cancer. However, we recently experienced a case in which two gastric tube ulcers occurred three months postoperatively; one penetrating into the pericardial cavity and the other into the left brachiocephalic vein. To our knowledge, no other such a case has ever been reported and we therefore report and discuss its etiology and management.

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.