Variations in survival and perioperative complications between hospitals based on data from two phase III clinical trials for oesophageal cancer.

BACKGROUND: Variations in institutional practice may contribute to different outcomes of cancer treatment. The impact of interinstitutional heterogeneity on outcomes between hospitals after oesophagectomy has not been examined previously using data from surgical clinical trials. METHODS: The data from two phase III trials for oesophageal cancer were used. Japan Clinical Oncology Group (JCOG) 9204 involved oesophagectomy (92-OP) versus oesophagectomy plus postoperative chemotherapy (92-POST), with accrual from 1992 to 1997. JCOG9907 involved postoperative chemotherapy (99-POST) versus preoperative chemotherapy (99-PRE), with accrual from 2000 to 2006. Hospitals contributing fewer than three patients were excluded. The influence of time and preoperative chemotherapy on interinstitutional heterogeneity related to postoperative complications and 5-year overall survival were evaluated by comparisons within and between these trial groups. Heterogeneity was estimated by a mixed-effects model after adjusting for age, sex, performance status, location of the primary tumour and clinical stage. RESULTS: Twelve hospitals in 92-OP (114 patients), 13 in 92-POST (114), 19 in 99-POST (158) and 18 in 99-PRE (154) were eligible. There was considerable heterogeneity in predicted postoperative complications in both groups in JCOG9204 (median 31.3 (range 15.0-68.2) per cent), and in 99-PRE (35.2 (22.6-46.6) per cent) but not in 99-POST (27.7 (27.7-27.7) per cent) from JCOG9907. A similar pattern was seen for predicted overall survival (92-POST: 66.4 (range 64.1-68.9) per cent; 99-PRE: 55.9 (54.0-59.7) per cent; 99-POST: 44.4 (44.4-44.4) per cent). CONCLUSION: Interinstitutional heterogeneity regarding complications and survival after oesophagectomy is a problem that merits wider consideration.

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.

Edaravone, a known free radical scavenger, enhances X-ray-induced apoptosis at low concentrations.

Edaravone has been reported to have a radioprotective effect at high concentrations. We now report that a lower dose of edaravone enhanced X-ray-induced apoptosis of some cell lines harboring p53 wild-type status, such as MOLT-4, Nalm-6, and HepG2. The knock-down of p53 using siRNA in MOLT-4 cells abolished the radiosensitizing effect of edaravone. Enhanced phosphorylations of p53 at Ser 15 and Ser 20 and up-regulation of PUMA, a p53 target protein, were observed after X-irradiation in the presence of edaravone. We conclude that the low dose of edaravone sensitized cells to X-irradiation by promoting the p53-dependent apoptotic signaling pathway.

The value of image coregistration during stereotactic radiosurgery.

BACKGROUND: Coregistration of any neuroimaging studies into treatment planning for stereotactic radiosurgery became easily applicable using the Leksell Gamma Knife 4C, a new model of gamma knife. The authors investigated the advantage of this image processing. METHOD: Since installation of the Leksell Gamma Knife 4C at the authors' institute, 180 sessions of radiosurgery were performed. Before completion of planning, coregistration of frameless images of other modalities or previous images was considered to refine planning. Treatment parameters were compared for planning before and after refinement by use of coregistered images. FINDINGS: Coregistered computed tomography clarified the anatomical structures indistinct on magnetic resonance imaging. Positron emission tomography visualized lesions disclosing metabolically high activity. Coregistration of prior imaging distinguished progressing lesions from stable ones. Diffusion-tensor tractography was integrated for lesions adjacent to the corticospinal tract or the optic radiation. After refinement of planning in 36 sessions, excess treated volume decreased (p = 0.0062) and Paddick conformity index improved (p < 0.001). Maximal dose to the white matter tracts was decreased (p < 0.001). CONCLUSION: Image coregistration provided direct information on anatomy, metabolic activity, chronological changes, and adjacent critical structures. This gathered information was sufficiently informative during treatment planning to supplement ambiguous information on stereotactic images, and was useful especially in reducing irradiation to surrounding normal structures.

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.

Concurrent chemoradiation alone with curative intent for limited-disease small-cell esophageal cancer in nine Japanese patients.

Small-cell carcinoma of the esophagus is a rare and aggressive tumor with early widespread dissemination. In this retrospective study, we report clinical outcomes of limited-disease small-cell carcinoma of the esophagus from the analysis of nine patients. Between 2003 and 2006, nine consecutive patients with small-cell carcinoma of the esophagus were treated in our single institution, representing 2.8% of all esophageal malignancies treated with curative concurrent chemoradiation during this period. All the patients received four cycles of etoposide (100 mg/m(2), days 1-3), combined with cisplatin (80 mg/m(2), day 1), plus radiation therapy (50 Gy in daily doses of 2 Gy, 5 days/week). At the time of analysis, the median follow-up time was 10.8 months (range: 4.2-42.8 months) and 21.8 months in five living patients (56%). Of all the nine patients, five patients (56%) had a complete response, and the actuarial 3-year overall survival rate was 55.6%. This regimen resulted in a favorable 3-year survival rate. We conclude that the optimum treatment seems to be the same as for small-cell carcinomas of the lung, that is, a multidrug combination chemotherapy regimen used with concurrent radiation.

Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for Japanese stage II-IV esophageal cancer compared with cisplatin plus 5-fluorouracil regimen: a retrospective study.

To evaluate the treatment outcome of radiotherapy combined with cis-diammine-glycolatoplatinum (nedaplatin) plus 5-fluorouracil (5-FU) for esophageal cancer. From January 2000 to December 2004, a total of 12 esophageal cancer patients with locally advanced and metastatic esophageal cancer (stages II-IVB) were treated with radiation therapy (50.4 Gy) combined with nedaplatin (80 mg/m(2), bolus infusion) and 5-FU (800 mg/m(2)/24 h, continuous infusion for 4 days) (NDP group). We compared the data with those of patients during the same period receiving a different chemotherapy regimen consisting of cisplatin (75 mg/m(2), bolus infusion) and 5-FU (1000 mg/m(2)/24 h, continuous infusion for 4 days) (n = 29, CDDP group) combined with the same radiation therapy. The median survival period was 11.5 months in the NDP group and 13.1 months in the CDDP group. The overall survival rates at 1-, 2-, and 3-years were 40%, 13%, and 13% in the NDP group and 56%, 42%, and 8% in the CDDP group (P = 0.2472), respectively. Grade III and IV leukocytopenia was observed in six (50%) and none of the patients in the NDP group and 14 (48%) and seven (24%) in the CDDP group, respectively. Grade III thrombocytopenia was observed in three (25%) in the NDP group and four (14%) in the CDDP group. Radiation combined with nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer. We recommend that NDP should be used rather than dose-reduction of CDDP combined with 5-FU in patients with impaired renal function as indicated by low creatinine clearance value (40-60 mL/min).

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.

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.

Characterization of the bi-directional transcriptional control region between the human UFD1L and CDC45L genes.

The human UFD1L and CDC45L genes, adjacently located in the head-to-head direction on chromosome 22q11, are separated by a 884 base-pair (bp) segment constituting the putative transcriptional control region. In this region we mapped one transcription start site at 69 bp upstream of UFD1L gene, and one major and one minor start sites at 76 bp and 503 bp upstream of CDC45L gene, which are to center in the putative core promoters designated as P(UFD1L), P(CDC45L/major), and P(CDC45L/minor), respectively. The three core promoters lacked a TATA-motif and had a high GC-content. To determine the approximate ranges for the regulatory promoters, the 884-bp fragment or those with a series of deletions were placed between firefly and renilla luciferase genes present in the head-to-head direction in a single plasmid, and the resulting plasmids were assayed for the two transiently induced enzyme activities. The P(UFD1L) and P(CDC45L/major) regulatory promoters were within 418 and 454 bp upstream of the respective start sites and their greater parts were not overlapping. The activity of P(CDC45L/minor) regulatory promoter was markedly enhanced when P(CDC45L/major) and its regulatory promoter were deleted. The deletion analyses revealed the basal activities of the three core promoters, which were enhanced by approximately twofold by the respective regulatory promoters, on the transfected DNA templates.

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.

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.

Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha.

Budding yeast CDC45 encodes Cdc45p, an essential protein required to trigger initiation of DNA replication in late G1 phase. We cloned four and one species of the human Cdc45p homolog cDNA, resulting from different splicing patterns, from HeLa cell and human placenta cDNA libraries, respectively. A comparison of the cDNAs and the genomic sequence showed that the longest encoding a 610-amino acid protein was comprised of 20 exons. One species, which lacks exon 7 and contains the shorter of two exons 18, was identical with the previously reported CDC45L cDNA and constituted 24 out of 28 clones from HeLa cells. Splicing was different in HeLa cells and TIG-1 cells, a human diploid cell line. Human CDC45 protein was found to bind directly in vitro to human minichromosome maintenance 7 protein (hMCM7) and to the p70 subunit of DNA polymerase alpha. The data support a thesis that human CDC45 acts as a molecular tether to mediate loading of the DNA polymerase alpha on to the DNA replication complex through binding to hMCM7.

A quantitative analysis of rat osteoporosis model with a microfocus X-ray tube and digital radiography system.

We have developed an X-ray magnification radiographic system incorporating a microfocus X-ray tube and an imaging plate in order to analyze the trabecular structure and mineral content of rat bone. Femoral bones of control, ovariectomy, and leuprorelin acetate depot rat groups were extracted and tested after the animals were sacrificed. Eleven water-equivalent phantoms, which contained hydroxyapatite at a density of 0 to 400 mg/cm3, were set around each femur and radiographed at the same time. The mean read-out signal intensity of the region of interest in the femur was converted to bone mineral density expressed in hydroxyapatite density through the use of a calibration curve relating the signal intensity to the hydroxyapatite density of the phantoms. The bone mineral density of the ovariectomy group was significantly lower than that of the control group, and no differences were found between the control and the leuprorelin acetate depot group. The present system is thought to be useful for quantitative evaluation of the mineral density of the rat femur.