Hoichi Kato

Evaluation of neck lymph node dissection for thoracic esophageal carcinoma

We studied a series of 150 patients treated for thoracic esophageal carcinoma at our institution. The patients were divided into two matched groups. Group B underwent transthoracic esophagectomy with mediastinal and abdominal lymphadenectomy only; group A also underwent bilateral neck lymph node dissection. The rates of operative mortality and operative complications did not differ significantly between the two groups. The 5-year survival rate was 38.7% overall (48.7% in group A and 33.7% in group B). Group A had a significantly better survival curve than group B. Twenty patients (26.0%) in group A had metastasis in the dissected neck lymph nodes. The 4-year survival rate of these patients was 47.9%. The significantly better survival of group A and the satisfactory prognosis in the patients with positive cervical lymph nodes demonstrates the effectiveness of neck lymph node dissection in radical operation for thoracic esophageal carcinoma.

Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases

No previous reports on lymph-node metastasis (LNM) from superficial squamous cell carcinoma of the esophagus have proposed definite criteria for additional treatment after endoscopic mucosal resection (EMR). We investigated the association between histopathological factors and LNM in 464 consecutive patients with superficial squamous cell carcinoma of the esophagus who had undergone a radical esophagectomy with lymph-node dissection (14 ‘M1’ lesions: intraepithelial tumors, 36 ‘M2’ lesions: tumors invading the lamina propria, 50 ‘M3’ lesions: tumors in contact with or invading the muscularis mucosa, 32 ‘SM1’ lesions: tumors invading the most superficial 1/3 of the submucosa and 332 ‘SM2/3’ lesions: tumors invading deeper than SM1 level). Histopathological factors including invasion depth, size, lymphatic invasion (LY), venous invasion, tumor differentiation, growth pattern, degree of nuclear atypia and histological grade were assessed for their association with LNM in 82 M3 or SM1 lesions to determine which patients need additional treatment after EMR. LNM was found in 0.0, 5.6, 18.0, 53.1 and 53.9% of the M1, M2, M3, SM1 and SM2/3 lesions, respectively. A univariate analysis showed that each of the following histopathological factors had a significant influence on LNM: invasion depth (M3 vs SM1), LY, venous invasion and histological grade. Invasion depth and LY were significantly associated with LNM in a multivariate analysis. Four out of 38 patients (10.3%) with M3 lesions without LY had LNM, whereas five out of 12 patients (41.7%) with M3 lesions and LY had LNM. Only patients with M1/2 lesions are good candidates for EMR. Invading the muscularis mucosa (M3) is a high-risk condition for LNM the same as submucosal invasion, but M3 lesions without LY can be followed up after EMR without any additional treatment.

Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma

OBJECTIVE Chemoradiotherapy is a popular definitive therapy for esophageal carcinoma among many patients and oncologists. Although the complete response rates are high and short-term survival is favorable after chemoradiotherapy, persistent or recurrent locoregional disease is frequent. Salvage surgery is the sole curative intent treatment option for this course of the disease. The present study evaluates the safety and value of salvage esophagectomy for locoregional failure after high-dose definitive chemoradiotherapy for esophageal squamous cell carcinoma. METHODS We reviewed 59 consecutive patients with thoracic esophageal squamous cell carcinoma who underwent salvage esophagectomy after definitive chemoradiotherapy. All patients received more than 60 Gy of radiation plus concurrent chemotherapy for curative intent. The data were compared with those of patients who received esophagectomy without preoperative therapy. RESULTS Postoperative morbidity and mortality rates were increased among patients who underwent salvage esophagectomy compared with those who underwent esophagectomy without preoperative therapy (mean hospital stay, 38 vs 33 days; anastomotic leak rates, 31% vs 25%; respiratory complication rates, 31% vs 20%; reintubation within 1 week, 2% vs 2%; hospital mortality rates, 8% vs 2%). Tracheobronchial necrosis and gastric conduit necrosis were highly lethal complications after salvage esophagectomy; 3-year postoperative survivals were 38% and 58%, respectively. CONCLUSION Patients who underwent salvage esophagectomy after definitive high-dose chemoradiotherapy had increased morbidity and mortality. Nevertheless, this is acceptable in view of the potential long-term survival after salvage esophagectomy. Such treatment should be considered for carefully selected patients at specialized centers.

A Phase II Trial of Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma: Japan Clinical Oncology Group Study (JCOG9708)

OBJECTIVE The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR). METHODS Patients with Stage I (T1N0M0) ESCC, aged 20-75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m(2) (day 1) and 5-FU 700 mg/m(2)/day (days 1-4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1-21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence. RESULTS From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6-94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3-89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3-78.8) (mucosal recurrence removed by endoscopy was not counted as an event). CONCLUSIONS High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.

Expression of E-Cadherin, α-Catenin, β-Catenin and Plakoglobin in Esophageal Carcinomas and Its Prognostic Significance

It has been suggested that inactivation of the cadherin-mediated cell-cell adhesion system plays a role in the initial steps of cancer invasion and metastasis. Expression of E-cadherin and its intracy

Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan

Introduction:  A dramatic increase in incidence of adenocarcinoma of the esophagogastric junction (EGJ) over the past two decades has been reported in the West. However, epidemiological data from Asian countries have not shown a similar trend. The aim of this study was to determine the incidence of adenocarcinoma of the EGJ in a cohort of consecutive patients operated on for gastric adenocarcinoma at a major cancer referral center in Japan.

Superficial esophageal carcinoma: Surgical treatment and the results

We report 92 patients treated with esophagectomy for superficial esophageal carcinoma (SEC; 9.1% of all resected esophageal cancers at our institution). the operative mortality rate was 5.4%. in 24 cases, cancer invasion was limited to the mucosa, and in 68 to the submucosa. Twenty‐three patients in the former group had no lymph node involvement, whereas 24 patients (35.3%) of the latter group had lymph node metastases. the 5‐year survival rate after surgery for patients with SEC limited to the mucosa was 83.5%, which was significantly better than that for carcinoma invading the submucosa (54.9%). No recurrent disease occurred in patients with lesions limited to the mucosa. in conclusion, an esophagectomy with wide lymphadenectomy is necessary to provide a better prognosis for SEC invading the submucosa, whereas a less extensive treatment may be considered for SEC limited to the mucosa.

The presence of aberrant DNA methylation in noncancerous esophageal mucosae in association with smoking history: a target for risk diagnosis and prevention of esophageal cancers.

Esophageal squamous cell carcinomas (ESCCs) tend to have multiple primary lesions, and it is believed that they arise from background mucosae with accumulation of genetic/epigenetic alterations. In this study, the objective was to elucidate the effects of smoking and drinking on the accumulation of epigenetic alterations in background mucosae.

Improved Survival for Patients With Upper and/or Middle Mediastinal Lymph Node Metastasis of Squamous Cell Carcinoma of the Lower Thoracic Esophagus Treated With 3-Field Dissection

Objective:To evaluate the outcomes with 2 and 3 lymph node dissection for patients with squamous cell carcinoma of the lower thoracic esophagus at a single institution. Background:Extensive lymph node dissection, including the upper mediastinum, for carcinoma of the lower thoracic esophagus is advocated as a standard surgical procedure with curative intent in Japan. However, its efficacy remains controversial. Methods:From January 1988 to December 1997, 532 patients with carcinomas of the thoracic esophagus underwent transthoracic esophagectomy and extensive lymph node dissection with curative intent at the National Cancer Center Hospital, Tokyo. Of these, 495 (93%) had squamous cell carcinomas. A total of 156 (29%) with tumors of the lower thoracic esophagus were retrospectively analyzed. Results:Of the 156 patients, 55 (35%) underwent 2-field and 101 (65%) underwent 3-field lymph node dissection. The operative morbidity and 30-day and in-hospital mortality rates were 68.0%, 1.3%, and 2.6%, respectively. The overall 5-year survival rate for the entire series was 49.3%. One hundred and seven (69%) had lymph node metastases. Upper and/or middle mediastinal lymph node metastases occurred in 42% of the series. The 5-year survival rate for patients with lymph node metastases in the upper and/or middle mediastinum was 23.3%. Among them, the values after 2- and 3-field lymph node dissection were 5.6% and 30.0%, respectively (P = 0.005). Thirteen (27%) of 48 patients with upper and/or middle mediastinal lymph node metastases treated with 3-field dissection had simultaneous cervical lymph node metastases and their 5-year survival rate was 23.1%. Conclusion:The 3-field approach for extensive lymph node dissection provides better survival benefit for patients with squamous cell carcinoma of the lower thoracic esophagus compared to 2-field lymph node dissection when lymph node metastases are present in the upper and/or middle mediastinum.

Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles

Background Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10−40 and OR=4.13, p=8.4×10−76, respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.