Pattern of lymph node metastases of esophageal squamous cell carcinoma based on the anatomical lymphatic drainage system.

The recent anatomical studies of the esophagus showed that submucosal longitudinal lymphatic vessels connect to the superior mediastinal and the paracardial lymphatics and lymphatic routes to periesophageal nodes originate from the muscle layer. Using clinical data for lymph node metastasis, we verify these anatomical bases to clarify the rational areas of lymph node dissection in esophageal cancer surgery. Analysis was performed on 356 consecutive patients who underwent esophagectomy with three-field dissection. Patients were divided into those with tumor limited within the submucosal layer and those with tumor invading or penetrating the muscle layer. Frequency of node metastasis was compared according to supraclavicular, upper mediastinum, mid-mediastinum, lower mediastinum, perigastric and celiac areas. In patients with tumor limited to the submucosal layer, node metastasis was more frequent in the upper mediastinum and perigastric area than the mid- or lower mediastinum. Even in patients with tumor located in the lower esophagus, node metastasis was more frequent in the upper mediastinum than the mid-mediastinum or lower mediastinum. In patients with tumor located in the mid-esophagus, node metastasis was more frequent in the supraclavicular area than the mid-mediastinum or lower mediastinum. In patients with tumor invading or penetrating the muscle layer, node metastasis in the mid- and lower mediastinum increased dramatically, but was still less frequent than those in the upper mediastinum or the perigastric area. Postoperative survival curves did not differ among the involved areas. The most predictive factor associated with lymph node metastasis for postoperative survival was not the area of involved nodes, but the number of involved nodes by multivariate analyses. These clinical results verify recent anatomical observations. The lack of difference in survival rates among the involved areas suggests that these areas should be staged equivalently. For adequate nodal staging, the upper mediastinum should be dissected for the lower esophageal tumor and supraclavicular areas should be dissected for the mid-esophageal tumor even in patients with tumor limited to within the submucosal layer.

Histological diversity in basaloid squamous cell carcinoma of the esophagus.

Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a distinct variant of esophageal cancer. This study investigated histopathological variations of BSCCE. Thirty-eight surgical and two endoscopically resected specimens of BSCCE were examined. Histological features were classified into five components: solid nest (SN), microcyst and/or trabecular nest (MT), ductal differentiation (DD), cribriform pattern (CP), and an invasive squamous cell carcinoma (SCC) component. The immunohistochemical phenotypes of each component were examined using antibodies against cytokeratin (CK) 7, CK14, and alpha smooth muscle actin (SMA). SN, MT, DD, CP, and SCC were present in 95.0, 97.5, 27.5, 32.5, and 82.5% of the cases, respectively, and combinations of SN & MT, SN & DD, SN, MT & DD, SN, MT & CP, and SN, MT, DD & CP were found in 50.0, 2.5, 10.0, 17.5, and 15.0%, respectively. All the intraepithelial lesions observed in 18 (45.0%) cases were SCC. Immunoreactivity for CK7, CK14, and SMA was seen in 10.5, 86.8, and 18.4% of SN; 30.8, 97.4, and 38.5% of MT; 54.5, 100.0, and 54.5% of DD; 7.7, 76.9, and 23.1% of CP; and 6.1, 97.0, and 0.0% of SCC, respectively. CK14 immunoreactivity was seen in the periphery of most of the SN component. CK7, CK14, and SMA immunoreactivity was seen in the inner layer, all layers, and the outer layer of DD, respectively. MT and CP showed partial peripheral positivity for CK14 and SMA in microcystic, trabecular, and cribriform-like pseudoglandular structures. BSCCE demonstrates various histopathological and immunohistochemical features including a ductal and cribriform growth pattern.

Predominant presence of Streptococcus anginosus in the saliva of alcoholics.

Chronic alcohol consumption is known to be a major risk factor for cancers of the upper aerodigestive tract. The incidence of esophageal cancer (4.4%) in alcoholics is reported to be much higher than that in the Japanese population as a whole (0.0001%). This suggests the presence of specific factors in chronic alcohol consumption-related carcinogenesis. Recently, data showing a significant correlation between Streptococcus anginosus and carcinogenesis in the upper aerodigestive tract have been reported. In this study, the ratio of S. anginosus to oral bacteria in the saliva of 38 alcoholic patients was investigated to determine if there is an association between alcoholic patients and S. anginosus infection. The level of S. anginosus in the saliva from 22 healthy people, 41 esophageal cancer patients, 32 gastritis patients, and 24 periodontitis patients was also investigated and compared to the level in alcoholic patients. In the saliva from esophageal cancer patients, the level of S. anginosus was not significantly different from that of healthy people. The levels of S. anginosus in periodontitis and gastritis patients were also similar. In alcoholics, however, there was an extremely high level of S. anginosus, suggesting that they, rather than healthy people and general esophageal cancer patients, have a high risk for S. anginosus infection.

Surgery for clinical T3 carcinomas of the upper thoracic oesophagus and the need for new strategies.

BACKGROUND: Patients with T3 carcinomas have a dismal prognosis, even after complete resection of the primary tumour and metastatic nodes. This study focused on the clinicopathological characteristics and outcomes after surgical resection of clinical T3 carcinomas of the upper thoracic oesophagus. METHODS: Between January 1988 and February 2000, 888 consecutive patients underwent surgical removal of carcinomas of the thoracic oesophagus or oesophagogastric junction at the National Cancer Centre Hospital, Japan. The case records of 51 consecutive patients with clinical T3 tumours of the upper thoracic oesophagus were analysed retrospectively. RESULTS: No patient received preoperative therapy. Complications occurred in 41 (80 per cent). In-hospital and 30-day postoperative mortality rates were 10 and 4 per cent respectively. Gross residual primary tumour or metastasis in regional nodes invading adjacent structures was noted in 14 patients (27 per cent) and incomplete resection including microscopic residual tumour in 23 (45 per cent). Overall 3- and 5-year survival rates were 20 and 12 per cent; median survival was 13.1 months. CONCLUSION: Surgical resection of clinical T3 carcinomas of the upper thoracic oesophagus is associated with a high postoperative complication rate, incomplete resection and unsatisfactory outcome. Reconsideration of the surgical treatment strategy for these tumours is needed.

Clinicopathologic characteristics and survival of patients with clinical Stage I squamous cell carcinomas of the thoracic esophagus treated with three-field lymph node dissection.

OBJECTIVE: Clinicopathologic characteristics and survival rates of patients with clinical Stage I tumors treated with three-field lymph node dissection have not been well investigated. This report documents the results of a series of cases of clinical Stage I squamous cell carcinomas treated with this surgical procedure in our institute. METHODS: From January 1988 to March 1997, 326 patients with carcinomas of the thoracic esophagus underwent transthoracic esophagectomy with three-field lymph node dissection. Two hundred and ninety-seven (91%) of these had squamous cell carcinomas. Fifty-seven (18%) patients with clinical Stage I squamous cell carcinomas of the thoracic esophagus were retrospectively reviewed here. RESULTS: Among 57 clinical Stage I squamous cell carcinomas, ten (18%) were diagnosed as T1-mucosal and 47 (83%) as T1-submucosal. Seventy percent of the patients with clinical T1-mucosal tumors had additional primary esophageal lesions. The operative morbidity and in-hospital mortality rates were 63 and 0%, and the overall 1-, 3-, 5-, and 10-year survival rates were 95, 86, 78, and 70%, respectively. Of the 57 tumors assessed pathologically, 12 (21%) were T1-mucosal, 42 (74%) were T1-submucosal, and three (5%) were T2. Nineteen (33%) exhibited lymph node metastasis. The 1-, 3-, 5-, and 10-year survival rates for patients with lymph node metastasis were 90, 79, 73, and 58%, respectively, as compared with 97, 90, 80, and 76, respectively for patients without lymph node metastasis (P=0.24). The accuracy of preoperative staging, based on both wall penetration and the status regarding lymph node metastasis, was 63%. With reference to the 1997 UICC-TNM staging system, 36 (63%) were pStage I, two (4%) were pStage IIA, 18 (28%) were pStage IIB, and three (6%) were pStage IVB. The 1-, 3-, 5-, and 10-year survival rates for patients with pStage I disease were 97, 92, 85, and 81%, respectively. In those with pStage II or IV disease, the values were 91, 76, 65, and 52%, respectively. CONCLUSIONS: Three-field lymph node dissection may be indicated even for patients with clinical Stage I squamous cell carcinoma requiring surgical intervention because this surgical procedure provides for possible cure by removing unsuspected lymph node metastasis.

Surgical therapy for recurrent esophageal cancers at anastomoses after esophagectomy.

BACKGROUND/AIMS: The long-term prognosis of a recurrent esophageal cancer at the anastomosis after esophagectomy is generally unfavorable. We have experienced six cases in our institute where surgical treatment resulted in a good prognosis. METHODOLOGY: Between 1962 and 1997, 1720 patients underwent esophagectomy for esophageal cancers in our institute. Anastomotic recurrence was identified in 13 and surgical therapy was performed for six of these. Their clinical and histopathological features were examined with reference to control of anastomotic recurrent esophageal cancers. RESULTS: The six patients were all males with an average age of 61.5 years. Their median disease-free interval was 5.5 months. Three patients lived more than five years after the first esophagectomy. Histopathologically, regional lymph node metastases were found in four of the cases and cervical lymph node metastases were detected in two at the initial esophagectomy. Vessel invasion was evident in three cases, intraepithelial spread in one, and multiple cancers in two. There were no cases with intramural metastasis. Radiotherapy and/or chemotherapy were added for three cases. CONCLUSIONS: After esophagectomy for esophageal cancers, frequent examination of the anastomotic site using endoscopy and long-term follow-up studies are desirable. The option of surgery should not be ignored when a recurrent cancer appears only at the anastomosis.

Three-field lymph node dissection for esophageal cancer in elderly patients over 70 years of age.

BACKGROUND: The risk and benefit of esophagectomy with three-field lymph node dissection has not been well defined in elderly esophageal cancer patients. METHODS: A total of 441 patients underwent three-field lymph node dissection from 1986 to 1998. Patients were divided into two age groups: group 1 consisted of 79 patients aged 70 years or over, and group 2 consisted of 362 patients under 70 years of age. Patients' characteristics and surgical outcomes were compared between groups. Risk factors for morbidity, mortality, and survival of patients in group 1 were further studied by multivariate analysis. RESULTS: Significantly more patients had multiorgan dysfunction preoperatively in group 1 (24; 30.4%) than in group 2 (34; 9.4%, p < 0.001). The overall (65.8% vs 61.6%, p = 0.483) and surgically related complication rates (41.8% vs 52.2%, p = 0.093) were similar, but significantly more organ failure (11.4% vs 5.0%, p = 0.031) and infection (22.8% vs 13.8%, p = 0.045), defined as medical complications, occurred in group 1. There was no significant difference in 30-day (3.8% vs 0.8%, p = 0.074) or in-hospital mortality (7.6% vs 3.3%, p = 0.082) between groups. The overall (40.9% vs 48.1%, p = 0.235) and cause-specific 5-year survivals (55.4% vs 59.1%, p = 0.688) were comparably good in both groups, but the risk of death due to causes other than esophageal cancer was much higher in the elderly (p = 0.028). Multiorgan dysfunction was an independent predictive factor in elderly patients for overall and medical morbidity, overall survival, and risk of death from causes other than esophageal cancer. CONCLUSIONS: Esophagectomy with three-field lymph node dissection could be carried out safely in patients over 70 years of age with satisfactory long-term results. For elderly patients with multiorgan dysfunction, however, less invasive procedures might be more appropriate.

Comparison of surgical management of thoracic esophageal carcinoma between two referral centers in Japan and China.

BACKGROUND: Comparison was made between two referral centers, the National Cancer Center Hospital (NCCH) in Japan and Shanghai Chest Hospital (SCH) in China. The aim was to detect the possible differences between surgical management of thoracic esophageal carcinoma in these two countries and to shed some light on how to improve the therapeutic outcomes at similar institutions. METHODS: A total of 98 patients (50 from NCCH and 48 from SCH) with squamous cell carcinoma of the thoracic esophagus treated by a single surgeon at either center during January 1997 to July 1999 were retrospectively reviewed. RESULTS: Lugol staining and endoscopic ultrasonography were applied routinely at NCCH only. More early diseases, multiple lesions and synchronous tumors of the digestive tract were detected in the NCCH group than in the SCH group. Significantly more stations of lymph nodes were dissected and higher metastatic rates to certain stations were found after more extensive lymphadenectomy in the NCCH group. Operation time was prolonged with significantly more postoperative complication but amount of blood loss or in-hospital mortality was not increased. There was a tendency toward better survival in the NCCH group at 2-year follow-up (70.9% NCCH vs. 56.2% SCH, p = 0.052). CONCLUSIONS: Lugol staining is useful in detecting early diseases or multiple lesions and endoscopic ultrasonography in increasing the knowledge of preoperative evaluation and thus should be recommended. Attention should be paid to more thorough lymph node dissection, especially those lymph node stations with high metastatic rates within the chest and the abdomen and meanwhile avoiding major postoperative complications, so as to improve further the accuracy of tumor staging and therapeutic outcome.

Prognostic evaluation for squamous cell carcinomas of the lower thoracic esophagus treated with three-field lymph node dissection.

OBJECTIVE: The efficacy of esophagectomy with three-field lymph node dissection in surgical treatment for patients with squamous cell carcinomas of the lower thoracic esophagus remains controversial. This report documents the outcomes of this surgical procedure for a large series. METHODS: From February 1986 to November 1998, 437 patients with squamous cell carcinomas of the thoracic esophagus underwent transthoracic esophagectomy with three-field lymph node dissection. One hundred and sixteen of these had cancer of the lower thoracic esophagus. To avoid the influence of adjuvant therapy on survival, 20 who also received radiation and/or chemotherapy were excluded, leaving 96 patients who were retrospectively analyzed. RESULTS: The operative morbidity, and 30-day and in-hospital mortality rates were 62, 0, and 3%, respectively. The overall 1-, 3-, and 5-year survival rates were 89, 65, and 59%, with a median survival of 76 months. In those with lymph node metastases (66% of cases), the values were 87, 56, and 48%, as compared with 94, 84, and 79%, respectively (P=0.005) for patients without lymph node metastasis. Factors significantly influencing the overall survival rates were patient age (> or = 65 vs. <65), clinical N status (cN1 vs. cN0), clinical M status (cM1 vs. cM0), longitudinal tumor length of resected specimen (> or =5 vs. <5 cm), pathologic T status (pT3 vs. pT1, 2), pathologic N status (pN1 vs. pN0), lymphatic invasion (positive vs. negative), vascular invasion (positive vs. negative) and intramural metastasis (present vs. absent). Independent prognostic factors for survival determined by multivariate analysis were pathologic T status (P=0.02), pathologic N status (P=0.03), and presence of intramural metastasis (P=0.04). Additional pathologic M1 status, cervical or celiac lymph node metastasis, was without significant influence. CONCLUSIONS: Patients with pathologic T3 tumors with both pathologic N1 status and the presence of intramural metastasis in the lower thoracic esophagus had a poor prognosis. Cervical or celiac lymph node metastasis in patients with carcinomas of the lower thoracic esophagus should be distinguished from pathologic M1 status in the UICC-TNM staging system.

Other primary cancers occurring after treatment of superficial oesophageal cancer.

BACKGROUND: Recent advances in endoscopic diagnosis and treatment have led to better prognosis for patients with superficial oesophageal cancer. The incidence of subsequent other primary cancer (SOPC) has become a new problem for patients who survive after treatment of superficial oesophageal cancer. METHODS: Between 1966 and 1998, 368 patients with superficial oesophageal cancer, histologically confirmed as squamous cell carcinoma after resection, were reviewed for the presence of SOPC. RESULTS: Among the 368 patients, 43 developed SOPC. The most frequent sites of SOPC were the stomach (11 patients) and hypopharynx (11). Subsequent cancers of the stomach and hypopharynx developed significantly more frequently in heavy smokers. The 5-year cumulative occurrence rate of subsequent cancers within the fields of endoscopy of the upper gastrointestinal tract (stomach, hypopharynx and residual oesophagus) was 15 per cent. CONCLUSION: Gastric and hypopharyngeal cancers were frequently found after resection of superficial oesophageal cancer. A history of heavy smoking at the time of initial resection may be a risk factor. To make an early diagnosis of subsequent cancers, follow-up observation by upper gastrointestinal endoscopy is important after treatment of oesophageal cancer.

Clinicopathological significance of tumor nest configuration in patients with esophageal squamous cell carcinoma.

BACKGROUND: Cancer-stromal interactions are an important mediator of cancer invasion and metastasis. METHODS: The authors investigated the clinicopathological significance of tumor nest configuration and the surrounding stroma in 159 patients with advanced esophageal squamous cell carcinoma (ESCC). The tumors were classified microscopically into two types. Type A tumors had oval-shaped or sheet-like tumor nests (with > 80% of the tumor area showing these features). Type B tumors had asteroid-shaped or scattered small tumor nests (with > 20% of the tumor area showing these features). RESULTS: Of the 159 tumors examined, 38 (24%) were type A and 121 (76%) were type B. Type B tumors had a significantly deeper invasion depth, more frequent lymphatic permeation and lymph node metastasis, more prominent active fibroblastic stroma, and less frequent inflammatory cell infiltration (P < 0.05). Both univariate (P < 0.05) and multivariate (P < 0.05) analysis of the patients' survival showed that the prognosis for patients with type B tumors was significantly worse than for patients with type A tumors. CONCLUSIONS: This study showed that tumor nest configuration, which corresponded to the behavior of tumor cells against stromal cells, correlated well with the aggressiveness of the tumor.

Clinicopathological study of multiple superficial oesophageal carcinoma.

BACKGROUND: Recently, the diagnosis of superficial oesophageal carcinoma has increased markedly in Japan as a result of advances in endoscopy. A number of these carcinomas have proved to be multiple. METHODS: Some 359 patients with superficial squamous cell carcinoma of the oesophagus who underwent oesophagectomy (n = 276) or endoscopic mucosal resection (EMR) (n = 83) were reviewed retrospectively. The clinicopathological features of patients with multiple superficial oesophageal carcinoma were compared with those of patients with a single superficial oesophageal carcinoma. RESULTS: Of the 359 patients, 99 (28 per cent) had multiple superficial oesophageal carcinoma. The male : female ratio in patients with multiple carcinoma was 98 : 1, compared with 5.3 : 1 for those with a single carcinoma (n = 260) (P = 0.0001). The incidence of tobacco and alcohol use was significantly higher in the patients with multiple carcinoma than in those with a single carcinoma (P = 0.04 and P = 0.03 respectively). The incidence of pharyngeal malignancy was also significantly higher in patients with multiple carcinoma (P = 0.02). CONCLUSION: The high incidence of multiple superficial oesophageal carcinoma indicates a need for careful evaluation of the oesophagus at the time of initial diagnosis, treatment and follow-up for superficial oesophageal carcinoma. Male sex, smoking, alcohol use and the presence of pharnygeal malignancy are high-risk factors for multiple superficial oesophageal carcinoma.

Preoperative chemotherapy for esophageal carcinoma with intramural metastasis.

BACKGROUND AND OBJECTIVES: The prognosis for patients with intramural metastasis (IMM) of esophageal cancer is poor. We examined the role of preoperative chemotherapy in the management of patients with this disease. METHODS: Fifteen patients with IMM of esophageal carcinoma received preoperative chemotherapy cisplatin on day 1 and 5-fluorouracil on days 1 to 5. This regimen was repeated after a 3-week interval, except in patients with progressive disease or severe toxicity who received only one cycle of chemotherapy. Patients underwent surgery around 3 weeks after completion of chemotherapy. Clinical response was evaluated and survival was compared with that of patients who did not receive preoperative chemotherapy. RESULTS: Toxicity was manageable except in one patient who experienced severe neurological adverse effect. The clinical response rate of the IMM was 66.7% (10/15) and the complete response rate was 6.7% (1/15); for the primary lesion, response rates were 86. 7% and 6.7%, respectively. All 15 patients underwent surgery. Seven of the 15 patients (46.7%) experienced non-fatal operative complications. The 5-year survival rate after surgery was 20%. CONCLUSIONS: Preoperative chemotherapy with cisplatin and 5-fluorouracil is feasible in patients with IMM of esophageal carcinoma. This regimen, however, does not improve survival and more effective treatment strategies are required.

A case of small polypoid esophageal carcinoma with multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components.

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.

Cervical lymph node metastasis in patients with submucosal carcinoma of the thoracic esophagus.

BACKGROUND AND OBJECTIVES: The effect of esophagectomy with three-field lymph node dissection for submucosal carcinoma of the thoracic esophagus remains controversial. The aim of this study was to evaluate the effect of esophagectomy with three-field lymph node dissection for submucosal carcinoma of the thoracic esophagus. METHODS: From January 1983 to December 1997, the records of 101 consecutive patients who underwent transthoracic esophagectomy with three-field lymph node dissection were retrospectively analyzed. RESULTS: The incidence of the operative complications was 70%. The 30-day and overall hospital mortality rates were 1.0% and 2.0%, respectively. The positive rate of histological cervical nodal metastasis was 17%. The 5-year survival rates for the patients with and those without cervical nodal metastasis were 55% and 71%, respectively. The difference between patients with and those without cervical nodal metastasis was not statistically significant. Cumulative 5-year survival rates for the patients with metastasis in the cervical, upper mediastinal, or abdominal lymph nodes were 55%, 65%, and 46%, respectively. There was no statistically significant difference between each survival. CONCLUSIONS: Three-field lymph node dissection may be indicated for patients requiring esophagectomy for submucosal carcinoma of the thoracic esophagus because the frequency of cervical lymph node metastasis is not negligible and acceptable overall hospital mortality and favorable survival rates of patients with histologically positive cervical nodes can be achieved.

Assessment of cervical lymph node metastasis in the staging of thoracic esophageal carcinoma.

BACKGROUND: Cervical lymph node metastases (CLM) from esophageal carcinoma are regarded as a part of the M component of the TNM classification. Patients with CLM, however, can experience extended survival after cervical lymph node dissection, unlike patients with other M components. METHODS: Among 844 patients with thoracic esophageal carcinoma, 197 underwent esophagectomy with three-field dissection of the cervical, mediastinal, and abdominal lymph nodes (3FD). The survival of patients with CLM was compared with that of patients with hematogenous metastasis (HM), and the prognostic value of CLM was assessed. RESULTS: The survival curve for patients with CLM was significantly better than that for patients with HM (P = 0. 002). Among the 197 patients who underwent 3FD, 46 (23.4%) had histologic CLM. Of the 165 patients without hematogenous metastases, 22 (13.3%) had histologic CLM. The survival curve for the patients with histologic CLM was not significantly differ from that for patients with mediastinal or abdominal lymph node metastasis (P = 0. 127, P = 0.155) by univariate analyses. CONCLUSIONS: The significantly better survival of patients with CLM compared with that of patients with HM strongly suggests that CLM carries a prognosis different from the other M components in the staging of thoracic esophageal carcinoma. Because the survival curve for patients after 3FD was similar to that of patients with metastasis in the mediastinum or abdomen, we feel CLM should be included in the N component.

Significance of involvement by squamous cell carcinoma of the ducts of esophageal submucosal glands. Analysis of 201 surgically resected superficial squamous cell carcinomas.

BACKGROUND: Ductal involvement (DI) is often observed in superficial squamous cell carcinoma of the esophagus (SSCCE), defined as carcinoma with invasion limited to the submucosa. The purpose of this study was to clarify the clinicopathologic significance of DI in SSCCE. METHODS: Two hundred one surgically resected lesions from 140 patients with SSCCE were examined histopathologically. Clinicopathologic factors, such as macroscopic type, tumor location, maximum tumor size, depth of invasion, lymphatic and blood vessel permeation, lymph node metastasis, and prognosis, were examined to investigate the association between these factors and the presence of DI. RESULTS: Of the 201 SSCCE lesions, 43 (21.3%) had 152 DIs (1-32 DIs per lesion). The DI always remained in situ, and there were no tumors showing submucosal invasion through the DI. As for the relation between clinicopathologic factors and the presence of DI, multivariate analysis showed only maximum tumor size to correlate with the presence of DI (P < 0.0001). There were no significant differences between DI negative and DI positive lesions in tumor location, macroscopic type, lymphatic and blood vessel permeation, lymph node metastasis, or prognosis. In 83 mucosal carcinomas, including in situ carcinomas or carcinomas that invaded no deeper than the lamina muscularis mucosa, no lymph node metastasis was found, and the 5-year survival rate was 100% (unaffected by the presence of DI). Among these 83 lesions, DI was found in 11 (13.8%), of which 6 (7.2%) had DI extending to the submucosal layer. CONCLUSIONS: These results indicate that DI as a pathway of tumor spread to the deeper layer is of little significance in squamous cell carcinoma of the esophagus, and that mucosal carcinomas with DI that extends to the submucosa should not be classified as submucosal carcinoma.

Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors.

BACKGROUND: If it were possible to elucidate the histopathologic findings predicting lymph node metastasis and prognosis in superficial squamous cell carcinoma of the esophagus (SSCCE), they could be used as markers to identify patients who do not require additional surgical resection after endoscopic mucosal resection (EMR). METHODS: Two hundred forty surgically resected SSCCEs were examined histopathologically. Histopathologic factors including vertical tumor invasion depth in the submucosal layer (VTIDsm), degree of nuclear atypia (low, one point; high, two points), growth pattern (expansive, one point; infiltrative, two points), and histologic grade (calculated by adding the latter two scores to obtain Grade 1, two points; Grade 2, three points; and Grade 3, four points) were evaluated to investigate the associations among these factors, lymph node metastasis, and prognosis. RESULTS: No lymph node metastasis was found in 54 patients with carcinoma limited to the lamina propria. Their 5-year survival rate was 100%. Multivariate analysis of 186 carcinomas invading beyond the lamina propria showed that lymphatic permeation correlated with lymph node metastasis (P<0.0001) and the presence of lymph node metastasis and a high histologic grade were independent factors indicating a poor prognosis (P = 0.0061 and 0.023, respectively). In 53 patients whose tumors had invaded the lamina muscularis or slightly invaded the submucosa (VTIDsm <500 microm), no lymph node metastasis was found in the lymphatic permeation negative and blood vessel permeation negative patients with VTIDsm values <200 microm and histologic Grades 1 or 2. CONCLUSIONS: Lymphatic permeation is a good predictor of lymph node metastasis in patients with SSCCE. Lymph node metastasis and the histologic grade are independent prognostic factors. Vessel permeation, VTIDsm, and histologic grade were found to be important factors for identifying patients who did not require additional surgical treatment after EMR.

Significance of extended systemic lymph node dissection for thoracic esophageal carcinoma in Japan.

In 1986, several institutions in Japan began to employ extensive lymphadenectomy for thoracic esophageal cancer. The aim of this article is to point out several confusing factors concerning the use of the terms "tow-field" and "three-field" lymph node dissection for thoracic esophageal cancer. In two-field nodal dissection, two components are included with (modern two-field) or without (traditional two-field) nodal dissection around both recurrent laryngeal nerve chains in the upper mediastinum. We studied a series of 353 patients resected for thoracic esophageal cancer in our institution. The patients were divided into three groups. Group A was the traditional two-field group of patients who underwent thoracoabdominal lymphadenectomy without upper mediastinal lymph node dissection after preoperative irradiation; group B was the modern two-field group, with additional upper mediastinal lymph node dissection; and group C was the three-field group with additional neck lymph node dissection. Groups B and C were operated on during the same period and did not received preoperative irradiation. The 5-year survival rate in group B was 54.9%, which was better than the 47.6% rate after three-field dissection (group C). The key to extensive lymphadenectomy for thoracic esophageal cancer does not lie in "cervical dissection" but in the meticulous dissection of the lymph nodes around the right and left recurrent laryngeal nerves.

Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma.

BACKGROUND: The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas. AIMS: To investigate whether CD44v, especially the CD44v2 (v2) isoform, may be a useful prognostic factor for patients with oesophageal squamous cell carcinoma, using a recently developed monoclonal antibody against a v2 epitope. PATIENTS: 233 patients (211 men and 22 women; mean age 61.9 years), with oesophageal squamous cell carcinomas curatively removed without additional treatment between 1987 and 1996 at the National Cancer Center Hospital, were analysed for CD44v expression. METHODS: The expression of CD44v was evaluated immunohistochemically using monoclonal antibodies against epitopes of the standard and variant protein, in paraffin embedded oesophageal squamous cell carcinoma tissue from 233 patients who had undergone cervical, mediastinal, and abdominal lymphadenectomy (three field dissection) for oesophagectomy. The data were evaluated for any correlation with clinicopathological indices or prognosis. RESULTS: Although total CD44 and CD44v6 (v6) were respectively observed in 99% and 97% of the cancer specimens, the expression of v2 was only 30%. Patients whose tumours were v2 positive had a significantly better prognosis than those whose tumours were v2 negative (p = 0.031). Furthermore, in patients without lymph node metastasis, v2 positivity alone was a significant independent factor of prognosis (relative risk of death associated with v2 negativity, 4.7; p = 0.037) in multivariate analysis. CONCLUSIONS: These results indicate that v2 is a useful marker for clinical prognosis in patients with oesophageal squamous cell carcinoma. Particularly in patients without lymph node metastasis, v2 status may thus have implications for the use of adjuvant chemotherapy and/or radiotherapy in patients with oesophageal cancer at an early stage.