Masamichi Baba

Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus.

ObjectiveThis study evaluated the impact of aggressive surgery on survival in patients with carcinoma of the thoracic esophagus. Summary Background DataPrognostic value of lymph-node status for patients with esophageal carcinoma was emphasized, although it is currently under debate whether extensive lymph node dissection improves survival. MethodsTwo hundred ninety-five patients with thoracic esophageal carcinoma were admitted to Kagoshima University Hospital from December 1982 to December 1990. Esophagectomy was performed on 244 (82.7%) of these patients; 106 of whom underwent three-field lymphadenectomy (bilateral cervical, mediastinal, and abdominal regions) were analyzed regarding lymph-node status, tumor recurrence, and the effect of prognostic factors on survival using Coxs proportional hazards model. ResultsHospital mortality and morbidity were 10.4% (11/106) and 65.1%, respectively. Seventy-eight patients (73.6%) had nodal involvement, including 49 patients with abdominal lymph-node metastases and 46 patients with recurrent nerve-node metastases. Five-year survival rates were 54.5% for 16 patients with a solitary nodal metastasis, 30.3% for stage III, 17.4% for stage IV, and 7.2% for 28 patients with six or more metastatic nodes. The most frequent sites of recurrence were the upper mediastinal region and the lung – its incidence increased significantly as the number of positive nodes increased. The most unfavorable prognostic factors included regional or recurrent nerve-node metastasis and patient age of more than 71 years. ConclusionsThree-field lymphadenectomy, including especially the removal of bilateral recurrent nerve nodes in the cervical region, is essential for improving the survival of patients with carcinoma of the upper two thirds of the thoracic esophagus.

Significant host- and tumor-related factors for predicting prognosis in patients with esophageal carcinoma

Objective To identify clinically useful parameters obtainable before treatment of predicting clinical outcomes in patients with esophageal carcinoma. Summary Background Data Various factors regarding the biologic state of tumors or the nutritional state of patients have been individually reported to correlate with prognosis. Reliable estimates of life expectancy before treatment are important, and consideration needs to be given not only to tumor-related but also to host-related factors in patients with esophageal carcinoma. Methods The following clinicopathological factors were retrospectively analyzed in 356 consecutive patients with surgical treatment: sex; age; serum C-reactive protein (CRP); proportion of lymphocytes; body weight changes; serum albumin; clinical TNM staging; tumor location; serum squamous cell-related antigen; serum carcinoembryonic antigen; and histology. Factors related to prognosis were evaluated by using univariate and multivariate analyses. Results According to univariate analysis, significant differences in survival were found for sex, serum CRP, proportion of lymphocytes, body weight change, serum albumin, serum squamous cell-related antigen, and clinical TNM staging. Multivariate analysis demonstrated that CRP levels (P = 0.0285), body weight change (P = 0.0165), and clinical TNM staging (P = 0.0008) displayed independent correlations to prognosis. When serum CRP elevation, body weight loss, and clinical TNM staging III and IV were scored as a combined index, the total score (prognostic index for esophageal cancer, PIEC) demonstrated a good stratification value for prognosis. Moreover, PIEC was superior to the conventional clinical TNM staging by the likelihood ratio test. Conclusions PIEC based on serum CRP, body weight change, and clinical TNM staging before treatment offers a very simple and informative method for predicting the prognosis of patients with esophageal carcinoma.

Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer.

AbstractBackground:The clinicopathologic significance of micrometastasis (MM) and tumor cell microinvolvement (TCM) in regional lymph nodes as identified by immunohistochemical staining for cytokeratin expression was evaluated in patients with node-negative gastric cancer. Methods:MM was defined as tumor cells with stromal reaction, and TCM was defined as individual tumor cells without stromal reaction. We investigated 1761 lymph nodes obtained from 67 gastric cancer patients whose diagnosis showed no lymph node metastasis by routine histological examination. The depth of tumor invasion was T1 (submucosa) in 33 patients and T2 (muscularis propria and subserosa) in 34 patients. The lymph nodes were examined immunohistochemically for the presence of tumor cells using anti-cytokeratin AE1/AE3 monoclonal antibody. Both the biopsy tumor specimens obtained prior to surgery and the resected primary tumors were immunostained with E-cadherin (E-cad) monoclonal antibody. Results:Thirty (1.5%) of the 1761 lymph nodes showed MM and/or TCM. MM with or without TCM was found in 10 patients, and TCM alone was found in 4 patients; 6 (18.2%) of the 33 patients with T1 tumor and 8 (23.5%) of the 34 patients with T2 tumor had occult lymph node metastasis. The 5-year survival rate was worse among those with MM with or without TCM, than among those without MM. Nearly all of the patients with MM and/or TCM had reduced or negative E-cad expression in the primary tumor. Conclusions:We demonstrated that the incidence of MM and/or TCM in the lymph nodes of patients with gastric cancer is quite high, and that such metastasis is associated with the prognosis of patients with pN0. Examination of E-cad expression in biopsy tumor specimens may be useful for predicting MM and/or TCM.

Surgical Maneuvers Enhance Molecular Detection of Circulating Tumor Cells During Gastric Cancer Surgery

ObjectiveTo evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. Summary Background DataSeveral studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase–polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. MethodsBlood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. ResultsCEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. ConclusionsA high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

Number of Lymph Node Metastases Determined by Presurgical Ultrasound and Endoscopic Ultrasound Is Related to Prognosis in Patients With Esophageal Carcinoma

ObjectiveTo analyze the impact on prognosis of the number of lymph node metastases detected by ultrasound and endoscopic ultrasound in patients with esophageal carcinoma. Summary Background DataUltrasound and endoscopic ultrasound are useful for diagnosing tumor depth and lymph node metastasis in patients with esophageal carcinoma. However, the clinical significance of the number of lymph node metastases before surgery has not been elucidated. MethodsThe authors evaluated lymph node metastases using preoperative ultrasound and endoscopic ultrasound in 329 consecutive patients who underwent esophagectomy with lymphadenectomy. TNM classification and one-to-one comparison of lymph node metastasis was performed between the preoperative and histologic diagnosis. The number of lymph node metastases was subdivided into four groups: zero, one to three, four to seven, and eight or more. ResultsThe accuracy of preoperative ultrasound and endoscopic ultrasound diagnosis exceeded 70% in each category of TNM classification. The incidence of lymph node metastasis determined by preoperative and histologic diagnosis was 69.0% (234/339) and 59.3% (201/339), respectively. The correlation between preoperative and histologic diagnosis was significant (P < .0001). According to the subdivision of number of lymph node metastases, the accuracy rates associated with nodal involvement of zero, one to three, four to seven, and eight or more were 83.8%, 59.7%, 43.3%, and 96.0%, respectively. The clinical outcome between ultrasound and endoscopic ultrasound diagnosis and histologic diagnosis in stage grouping was almost similar. The 5-year survival rates of patients with zero, one to three, four to seven, and eight or more lymph node metastases determined by ultrasound and endoscopic ultrasound were 53.3%, 33.8% 17.0%, and 0%, respectively. The differences among groups were statistically significant. The survival curves associated with preoperative and histologic diagnosis were similar. ConclusionsNot only the stage grouping of TNM classification but also the number of lymph node metastases determined by ultrasound and endoscopic ultrasound before surgery may be useful for predicting prognosis in patients with esophageal carcinoma.

Appraisal of Ten-Year Survival following Esophagectomy for Carcinoma of the Esophagus with Emphasis on Quality of Life

Abstract. Characteristics of 10-year survival after esophagectomy for carcinoma were studied retrospectively in 161 patients who underwent curative operation between 1973 and 1984. Of the 161 patients, 44 (27.3%) survived for 10 years after operation (right transthoracic approach with cervical anastomosis in 36 patients and left thoracoabdominal approach with jejunoesophagostomy in 8 patients). Females survived significantly longer than males; 10-year survival was observed in 10 (50%) of 20 females and 34 (24.1%) of 141 males. TNM factors were significantly linked to the 10-year survival for 25 patients (56.8%) whose tumors invaded the adventitia and 20 patients (45.5%) who had lymph node metastases, where the total number of involved nodes was less than eight. A questionnaire mailed 10 years after operation revealed that about one-fifth of the 10-year survivors could not go up one flight of stairs without taking a rest, and that the daily activity significantly deteriorated if the patient’s age at the time of surgery was more than 66 years. One-third of the 10-year survivors were not satisfied with the daily quantity of food intake, resulting in no gain of body weight after discharge from the hospital. This complaint was significantly correlated with either weekly reflux or heartburn, resulting in the increasing number of nonmalignancy deaths. Of 13 ten-year survivors who were alive at 10 years but died after that, 11 (84.6%) died of pneumonia or malnutrition. Duodenogastroesophageal reflux may eventually cause nonmalignancy death 10 years after esophagectomy for carcinoma.

Detection and Clinical Significance of Lymph Node Micrometastasis Determined by Reverse Transcription-Polymerase Chain Reaction in Patients with Esophageal Carcinoma

We investigated micrometastasis in lymph nodes by detecting carcinoembryonic antigen (CEA) mRNA. A total of 400 lymph nodes obtained from 21 patients with esophageal carcinoma were examined by CEA-specific reverse transcription-polymerase chain reaction (RT-PCR). Serial sections of positive lymph nodes were reexamined histologically and immunohistologically. Twenty-seven lymph nodes of 11 patients were diagnosed as being positive by conventional histologic examination. CEA-mRNA positivity was found in 18 of 21 patients. Among 373 histologically negative nodes, 79 (21.2%) were positive for CEA mRNA. Of these, micrometastasis was detected in 2 by histological reexamination and in 11 by immunohistochemical staining using cytokeratin antibody. Two of 6 RT-PCR-positive patients (33.3%) had recurrent disease. Four of 11 patients (36.4%) whose nodal involvement was discovered by routine histological examination also had recurrent cancer. CEA-specific RT-PCR detected micrometastasis in lymph nodes at a higher rate than histological or immunohistochemical analysis of serial sections. Since the incidence of CEA-mRNA positivity is high in the lymph nodes of esophageal cancer patients except for those with early cancer, these patients should be treated with adjuvant therapy.

Thymidine phosphorylase in human esophageal squamous cell carcinoma

Experimental evidence has shown that thymidine phosphorylase (dThdPase) is identical to platelet‐derived endothelial cell growth factor (PD‐ECGF) and has angiogenic activity. The enzymatic activity of dThdPase was needed for the angiogenesis by the enzyme. These observations were catalysts for the current study.

Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma

The lymph nodes of 59 patients with pN0 esophageal squamous cell carcinomas were examined immunohistochemically using cytokeratin (CK) antibody. Primary tumors were immunostained with cyclin D1 (CD1) and E-cadherin (E-cad) antibody. Lymph node micrometastasis (MM) was found in 39 (55.5%) patients. Tumor recurrence was found in 17 patients and all but one of them had MM. The 5-year survival rate was significantly poorer in patients with MM than in those without MM. Almost all patients with positive CD1 and negative E-cad expression had MM. The examination of CD1 and E-cad expression in primary tumors may be useful for predicting MM.

Assessment of cervical lymph node metastasis in esophageal carcinoma using ultrasonography.

OBJECTIVE To evaluate the efficacy of ultrasonography for the diagnosis of cervical lymph node metastasis in esophageal carcinoma. SUMMARY BACKGROUND DATA Ultrasound (US) examination is useful for diagnosing lymph node metastasis. However, few reports have examined its role in the decision to perform cervical lymph node dissection in esophageal carcinoma. METHODS Ultrasound examination was performed to evaluate cervical lymph node metastasis in 519 patients with esophageal carcinoma. The patients were divided into 5 groups according to treatment received: group 1, 153 patients who underwent curative resection of primary tumor by right thoracotomy and complete bilateral cervical lymphadenectomy; group 2, 112 patients who underwent curative resection of primary tumor by right thoracotomy but without cervical lymphadenectomy; group 3, 78 patients who underwent esophagectomy by left thoracotomy or blunt dissection with or without removal of cervical lymph nodes; group 4, 76 patients with palliative resection without cervical lymphadenectomy; and group 5, 100 patients without any surgical treatment. US diagnosis was compared with histologic findings or cervical lymph node recurrence. RESULTS Lymph node metastasis was detected in 30.8% of patients (160/519). The sensitivity, specificity, and accuracy of US diagnosis in group 1 were 74.5%, 94.1%, and 87.6%, respectively. Cervical lymph node recurrence was seen in 7 patients (4.6%) in group 1, in 4 patients (3.6%) in group 2, and 3 patients (3.8%) in group 3. Although the incidence of cervical lymph node metastasis as determined by US examination was high in groups 4 and 5, almost none of the patients died of cervical lymph node metastasis. CONCLUSIONS Ultrasound examination plays a useful role in the decision to perform cervical lymph node dissection in patients with esophageal carcinoma, particularly in those with potentially curative dissection.