Mario Shimada

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.

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.

Occult Lymph Node Metastasis in Gastric Cancer with Submucosal Invasion

To evaluate more precisely the incidence of lymph node metastasis in patients with submucosally invaded (sm) gastric cancer, three additional sections were made from the remaining half of 1,794 lymph nodes taken from 57 patients, for a detailed reexamination. Lymph node metastasis was demonstrated in 19 nodes from 11 patients by the initial routine examination; however, the detailed reexamination showed cancer involvement in a further nine lymph nodes from eight patients. Of these eight patients, metastasis had not been detected in any lymph nodes by routine examination in six. Macroscopically, the lesion was of the depressed or mixed type in six of the eight patients. From the intranodal location and growth pattern of the cancer foci, lymph nodes with occult metastasis were divided into the marginal sinus type, the medullary sinus type, and the mixed type, with the marginal type being found most frequently. The overall incidence of lymph node metastasis in patients with sm gastric cancer was as high as 29.8% (17/57) in this series. Moreover, a follow-up study revealed that two patients with occult metastasis died of cancer recurrence postoperatively. Accordingly, systematic regional lymph node dissection should be carried out at the time of surgery for sm gastric cancer.

Mucosal Squamous Cell Carcinoma of the Esophagus: A Clinicopathologic Study of 30 Cases

A clinicopathologic study was carried out on 30 patients with mucosal esophageal cancer (MEC). The depth of cancer invasion was subdivided histologically into three categories: m1 = carcinoma in situ (intraepithelial carcinoma) or carcinoma with questionable invasion beyond the basal membrane; m2 = cancer invasion confined to the lamina propria, and m3 = cancer reaching to or infiltrating into the muscularis mucosae. Lymph node metastases and lymphatic invasion were found only in the tumors reaching or infiltrating the muscularis mucosae (m3). The maximum histologic vertical extent of the tumors was more than 1 mm in 4 of 5 patients with lymph node metastasis or lymphatic invasion. None of the patients died of recurrent esophageal disease, and 3 of the 6 patients who had a second primary tumor died of this other malignancy. It is critical to distinguish between m1, m2 and m3 tumors to plan a treatment strategy, including an endoscopic mucosal resection.

So-called carcinosarcoma of the esophagus: A clinicopathologic, immunohistochemical and DNA flow-cytometric analysis of 6 cases.

Six cases of carcinosarcoma of the esophagus were studied clinicopathologically, immunohistochemically and with DNA flow cytometry. Transitional areas with morphology intermediate between carcinoma and sarcoma were found microscopically in all cases. Immunohistochemically, the carcinomatous areas contained keratin-positive cell components in all cases while vimentin-positive cells were found in sarcomatous areas in 5 cases. By DNA flow analysis of microdissection, the sarcomatous components of the tumors showed an aneuploid pattern with one exception, in contrast the carcinomatous components were diploid in all cases. In these few cases, PCNA, S-phase fraction and the mitotic rate were extremely high, apparently indicating a correlation with malignant behavior. Accordingly, examination by immunohistochemistry and DNA ploidy is useful for the analysis of biological properties in the so-called carcinosarcoma of the esophagus.

Lymph node and perinodal tissue tumor involvement in patients with esophagectomy and three‐field lymphadenectomy for carcinoma of the esophagus

Lymph node metastasis is a definitive prognostic factor; however, perinodal fat tumor invasion has not been fully elucidated.

Design and testing of a new cisplatin form using a base material by combining poly-D,L-lactic acid and polyethylene glycol acid against peritoneal metastasis.

Microspheres containing cisplatin (CDDP) embedded in poly‐d,l‐lactic acid (PLA) and polyethylene glycol acid (CDDP‐PPMS) were developed to improve treatment of malignant effusions. In vitro studies demonstrated that CDDP was released continuously for more than 4 weeks from CDDP‐PPMS without initial burst. CDDP‐PPMS was compared with CDDP aqueous solution (CDDP‐SOL) by i.p. administration in rats for 1) tissue distribution, 2) toxicity and 3) therapeutic effects against Yoshida sarcoma. We found that the CDDP concentration in the omentum was maintained at a higher level than in the CDDP‐SOL group, while the particles of CDDP‐PPMS were observed in the stomata of the omentum by electron microscopy. Concentrations of CDDP in the lung, liver, kidney and blood were lower in the CDDP‐PPMS group than in the CDDP‐SOL group. All rats given CDDP‐PPMS containing ≤28 mg/kg were alive, whereas in the CDDP‐SOL group, all rats given ≥16 mg/kg died from side effects. The LD50 of CDDP‐PPMS and CDDP‐SOL were 32.8 and 14.8 mg/kg, respectively. The survival of rats with peritoneal metastasis was better in the CDDP‐PPMS group than in the CDDP‐SOL group. Int. J. Cancer 76:709–712, 1998.© 1998 Wiley‐Liss, Inc.

Endosonographic detection of mediastinal lymph node metastasis in superficial carcinoma of the esophagus: assessment by type classification and histogram.

BackgroundEndoscopic ultrasonography (EUS) has been shown to be useful for detecting lymph node metastasis in esophageal cancer. The evaluation of nodal metastasis requires both objective and subjective analyses. In the present study, mediastinal lymph nodes in superficial esophageal carcinoma (SEC) were examined by both EUS appearance and histography, using NIH image software.MethodsOne hundred and seventy-one lymph nodes of 56 patients with SEC were detected by EUS. These lymph nodes were diagnosed by type classification, based on boundary and internal echo, and by the construction of internal echo histograms using NIH image software. The results were compared with the histological findings.ResultsThe sensitivity, specificity, and accuracy in assessing mediastinal lymph node metastasis by type classification were 83.3%, 88.2%, and 87.7%, respectively. The mean and SD of the histogram correlated well with histological findings and type classification (P < 0.0001). All lymph nodes with a mean value of less than 185 of the histogram were negative nodes. When positive nodes by type classification were reevaluated according to the threshold value of 185 using the histogram, the sensitivity, specificity, and accuracy improved to 83.3%, 100%, and 98.2%, respectively.ConclusionsType classification assisted by histography improved the diagnostic accuracy of mediastinal lymph node metastasis in SEC.

Biological evaluation of undifferentiated carcinoma of the esophagus

BackgroundPatients with undifferentiated carcinoma of the esophagus (UEC) are rare and have a poor prognosis compared with those with differentiated squamous cell carcinomas (DECs). We compared clinicopathological and biological features of UEC and DEC, with emphasis on markers for epithelial cell origin, proliferation, and cell-cell adhesion.MethodsSeven patients with UEC were compared with 21 with DEC. Immunohistochemical studies were performed by using monoclonal antibodies to cytokeratin, epithelial membrane antigen, p53, p21WAF1/CIP1, Ki-67, E-cadherin, desmoglein-1, and thrombomodulin.ResultsPatients with UEC had a poorer prognosis because of hematogenous metastasis at the time of presentation (mean survival, 6.5±6.2 vs. 35.5±28.9 months;P<.05). Immunohistochemical findings for cytokeratin and epithelial membrane antigen suggest that some UECs had epithelial origins. The following immunohistochemical profile of UEC was consistent with its highly malignant properties: (1) reduced or negative expression of cell-cell adhesion molecules such as E-cadherin, desmoglein-1, and thrombomodulin, (2) high positive rate for p53 and Ki-67, and (3) negative expression of p21WAF1/CIP1.ConclusionsThe immunohistochemical findings for UEC showed its high cell-proliferative activity and a high potential for metastasis. Clinical features of UEC were supported by the results of immunohistochemical findings.