Expression and prognostic significance of EFNB2 and EphB4 genes in patients with oesophageal squamous cell carcinoma.

OBJECTIVE: Tyrosine kinases and its receptors play important roles in growth, migration, and invasion of malignant cells. Among those, there are only few reports examining the expression pattern of Eph/ephrin signalling system in oesophageal carcinoma. The prognostic importance of ephrin-B2 ligand (EFNB2) and its receptor EphB4, and its correlation with clinicopathologic characteristics are yet to be delineated in patients with oesophageal carcinoma. MATERIALS AND METHODS: EFNB2 gene and EphB4 receptor gene were examined of mRNA specimens in 61 patients with oesophageal squamous cell carcinoma using reverse-transcriptase polymerase chain reaction. EFNB2 protein was selectively examined using an immunohistochemical analysis. RESULTS: EFNB2 mRNA expression was detected in 38 (62.3%) and EphB4 expression was found in 44 (72.1%) out of 61 cancer tissues analysed. There was a statistically significant correlation between EFNB2 expression and number of lymph node metastasis (P<0.05), and a trend toward statistical significance for correlation between EFNB2 expression and American Joint Committee on Cancer Classification Stage (P<0.1), indicating that EFNB2 expression was up-regulated by advancement of the disease process. EFNB2 protein was strongly expressed in tumour with high mRNA EFNB2 expression and was weakly expressed in tumour with low mRNA expression in some representative tumours. The 5-year overall survival rate (23%) of patients with positive EFNB2 gene expression was significantly worse than 55% of negative expression (P<0.05). The results of multivariate analysis of prognosticators for survival showed that positive EFNB2 gene expression (P<0.01) and number of lymph node metastasis (P<0.05) were identified as significant factors indicative of a poorer survival. CONCLUSIONS: EFNB2 gene expression may be a biological marker and a useful prognostic indicator in patients with oesophageal squamous cell carcinoma.

Parental presence during induction enhances the effect of oral midazolam on emergence behavior of children undergoing general anesthesia.

BACKGROUND: Pre-anesthetic anxiety and emergence agitation are major challenges for anesthesiologists in pediatric anesthesia. Thus, sedative premedication and parental presence during induction of anesthesia (PPIA) are used to treat pre-anesthetic anxiety in children. The aim of the present study was to test if a combination of mother presence and midazolam premedication is effective for improving emergence condition in children undergoing general anesthesia. METHODS: Sixty children were allocated to one of three groups: a sedative group (0.5 mg/kg oral midazolam), a PPIA group or a sedative and PPIA group. When anesthesia was induced with 7% sevoflurane in 100% oxygen, qualities of mask induction were rated. Anesthesia was maintained with sevoflurane (1.5-2.5%) in 60% oxygen and intravenous fentanyl 4 microg/kg. During emergence from anesthesia, the score of the child's emergence behavior was rated. RESULTS: The children in the midazolam group showed a better quality of mask induction compared with those in the PPIA group, the addition of parental presence to oral midazolam did not provide additional improvement of mask induction. In contrast, the children in the midazolam + PPIA group were less agitated than those in the other groups at emergence from anesthesia. CONCLUSION: Parental presence during induction of anesthesia enhanced the effect of oral midazolam on emergence behavior of children undergoing general anesthesia.

Aspirin and indomethacin for the prevention of experimental port-site metastases.

BACKGROUND: Nonsteroidal antiinflammatory drugs have been shown to have antitumor and chemopreventative effects. We investigated the potential of these drugs to inhibit port-site and intraperitoneal metastases. METHODS: The antiproliferative effect of aspirin and indomethacin on tumor cells was measured in vitro and in vivo. The in vivo experiments used DA rats to measure the effects of aspirin and indomethacin on the development of port-site metastases and the proliferation of intraperitoneal tumor cells after laparoscopy. RESULTS: In vitro, aspirin and indomethacin had an antiproliferative effect on tumor cells, inhibiting cell division and killing cells in a concentration and time-dependent manner. Orally administered aspirin and indomethacin, at the maximum tolerated dose, did not reduce the rate of intraperitoneal tumor cell division and had no effect on peritoneal metastases, or the number or size of port-site metastases. CONCLUSIONS: Despite promising in vitro studies, this study does not suggest there will be any clinical therapeutic value associated the use of aspirin or indomethacin for the prevention of the spread of tumor following the spillage of cells into the peritoneal cavity at laparoscopic surgery.

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences. Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.

Impact of splenectomy on the early outcome after oesophagectomy for squamous cell carcinoma of the oesophagus.

AIM: Operative procedures for oesophageal malignancies are becoming more extensive and may result in fatal complications. Splenectomy compromises the immune system and can lead to increased susceptibility to infections. The aim of the present study was to report the early outcome of patients who underwent oesophagectomy and simultaneous splenectomy due to oesophageal squamous cell carcinoma (SCC). METHODS: Pre-operative risks and post-operative morbidity and mortality in 135 patients who had undergone extensive oesophagectomy without simultaneous splenectomy for SCC of the thoracic oesophagus were compared with those of 14 patients who had undergone oesophagectomy associated with splenectomy. RESULTS: Post-operative pneumonia, intra-abdominal abscess, post-operative sepsis and anastonotic leakage were significantly increased when splenectomy was added to the original operation. The incidence of in-hospital death was significantly higher among splenectomized than non-splenectomized patients (35.7% vs 8.1%, P<0.01). Pulmonary complications and leakage were the main causes of death. Multivariate analysis recognized splenectomy as an independent prognostic factor for in-hospital death following transthoracic oesophagectomy for SCC. CONCLUSION: The addition of splenectomy to transthoracic oesophagectomy for oesophageal carcinoma can be a fatal combination. Preservation of the spleen should be the primary intention. In circumstances that necessitate splenectomy precautions should be taken to prevent post-operative infectious complications.

A new procedure for chronic atrial fibrillation: bilateral appendage-preserving maze procedure.

BACKGROUND: Atrial transport and atrial natriuretic peptide secretion is severely reduced from normal after the maze III procedure. To improve these factors, we developed a bilateral appendage-preserving maze procedure (BAP-maze). METHODS: Forty-six patients with chronic atrial fibrillation who underwent the BAP-maze procedure were compared with 40 patients who underwent the maze III procedure. The ratio of the peak velocity of the A and E waves of transmitral flow (transthoracic pulsed Doppler echocardiography), the left atrial appendage ejection fraction (transesophageal echocardiography), and the atrial natriuretic peptide secretory reserve during treadmill exercise test were measured at 6 months postoperatively. RESULTS: Sinus rhythm was restored in 44 patients (95.7%) by the BAP-maze procedure and in 39 patients (97.5%) by the maze III procedure. The ratio of the peak velocity of the A and E waves was 0.52 +/- 0.22 in the BAP-maze group and 0.25 +/- 0.19 in the maze III group (p < 0.0001). The left atrial appendage ejection fraction was 44.7% +/- 11.5%, and the atrial natriuretic peptide secretory reserve was greater in the BAP maze group (p = 0.037). CONCLUSIONS: The BAP-maze procedure improved atrial transport and atrial natriuretic peptide secretion as well as simplifying the maze operation, without decreasing its effectiveness against atrial fibrillation.

Esophagectomy and hepatic arterial chemotherapy following hepatic resection for esophageal cancer with liver metastasis.

We report a patient who had simultaneous transthoracic esophagectomy and hepatic arterial cannulation for chemotherapy following hepatic resection for esophageal cancer with solitary liver metastasis. He had an uneventful postoperative course and received two cycles of postoperative arterial chemotherapy with cisplatinum and 5-fluorouracil. He developed multiple liver metastases 6 months after the surgery. He has been receiving arterial chemotherapy at the outpatient department and is alive 15 months after the surgery. Aggressive esophagectomy and hepatic arterial chemotherapy is the treatment of choice for esophageal cancer with liver metastasis when unresectable metastases are confined to the liver.

Dukes' classification as a useful staging system in resectable squamous cell carcinoma of the esophagus.

Dukes' classification for colorectal cancer is simple and has been widely used as a valuable prognostic indicator. It has been used as an assessment of gastric cancer, but it has not been evaluated for esophageal cancer. Of 251 patients with primary squamous cell carcinoma of the thoracic esophagus between February 1981 and April 1999, 155 patients underwent esophagectomy with a curative intent. Clinicopathologic characteristics of those 155 patients were retrospectively investigated according to the Dukes', tumor node metastasis (TNM) and Japanese staging systems. Dukes' classification showed a clear correlation between tumor stage and survival. The 3-year and 5-year survival rates of 64 Dukes' A cases were excellent (97.4% and 93.7%), good for 12 Dukes' B (75% and 75%), and poor for 79 Dukes' C (50.5% and 43.4%), respectively (P < 0.05; Dukes' A vs B, P < 0.0001; Dukes' A vs C, P < 0.10; Dukes' B vs C). TNM stage classification also showed a good correlation between tumor stage and survival, but there were no significant differences between stage 0, I and stage IIA cases (P = 0.2678) and between stage III and stage IV cases (P = 0.8298). In the Japanese staging system, there were no significant differences among stage 0, stage 1, and stage 2 cases (P = 0.4093). Dukes' classification was significantly correlated with tumor size, Borrmann type, histological type, and vessel invasion. Subdivision of Dukes' C according to the number of positive lymph nodes (1-4 vs > or = 5) showed a clearer correlation with survival rather than other subdivisions, such as the metastatic lymph node ratio (< 1.0 vs > 1.0) or the site of lymph node metastasis. Dukes' classification, which incorporates the number of positive lymph nodes, correlates well with tumor progression and provides a simple useful staging system after curative esophagectomy for esophageal cancer. Dukes' A tumor could be proposed as a criterion of early esophageal carcinoma.

Early and late outcomes after reoperation for prosthetic valve endocarditis.

OBJECTIVE: Prosthetic valve endocarditis remains a challenging complication after heart valve replacement. To identify predictive risk factors, we have reviewed 30 patients who underwent surgery for prosthetic valve endocarditis between March 1986 and May 1999. METHODS: There were 15 men and 15 women (mean age 51 years). Prosthetic valve endocarditis was classified as early (< or = 1 year after operation) in 10 cases, and as late in the other 20 cases. The most common indication for surgery was moderate to severe congestive heart failure due to prosthetic valve dysfunction in 21 (70%) patients. The average follow-up period was 6.5 years, with a range of 0.3 to 14.1 years. RESULTS: The most common microorganism was Staphylococcus epidermidis in both patients with early (50%) and late prosthetic valve endocarditis (25%). The in-hospital mortality was 13.3% (4/30). There were six late deaths. The actuarial survival at 5 years was 78% and 66% at 10 years. An early onset of prosthetic valve endocarditis was the only significant determinant of both in-hospital mortality (p = 0.005) and overall mortality (p = 0.021). Emergency surgery had a statistically significant relationship with in-hospital mortality (p = 0.045). No significant influence on mortality after reoperation for prosthetic valve endocarditis was found in age, sex, valve position, antecedent native valve endocarditis, or in the type of pathological findings (ring abscess, valve dehiscence, and vegetation). CONCLUSION: Early onset of prosthetic valve endocarditis and emergency surgery were important risk factors for mortality due to prosthetic valve endocarditis.

[Plication of the sinotubular junction for aneurysm of the ascending aorta associated with aortic regurgitation: a case report].

A 63-year-old woman with aneurysm of the ascending aorta associated with AR due to dilatation of the sinotubular junction (STJ) and with poor LV function, who did not have Marfan syndrome, underwent a plication of the STJ and replacement of the ascending aorta. In operation, we simultaneously performed the plication of dilated STJ (60 mm) and the replacement of ascending aorta using a 26 mm Woven Dacron graft. Post-operative angiogram (1 POM) showed no aortic regurgitation and good recovery of the LV function. This procedure is less invasive, and indicated for patients without significant elongation or thickening of the aortic valve, especially when the patients have higher risk.

Prognosis of T4 gastric carcinoma patients: an appraisal of aggressive surgical treatment.

BACKGROUND AND OBJECTIVES: Despite precipitous drop in the incidence of gastric carcinoma in Japan, it is still one of the leading causes of death associated with malignant disease. Once the contiguous organs are involved the prognosis becomes dismal. Prognostic factors governing the survival of patients with T4 gastric carcinoma remain unclear. METHODS: Between 1980 and 1998, 150 patients were treated for T4 gastric carcinoma. Results and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: With a 73% resectability, patients with tumor resection had a significantly (P < 0.0001) improved survival rate. Within an acceptable operative mortality (2.6%), apparently curative cases had survival benefit (P < 0.0001) over noncurative cases. In the multivariate analysis, the death risk increased by 2.18 (relative risk) when splenectomy was spared from the operative procedure (P < 0.0071). Presence of esophageal invasion was the other independent prognostic factor in T4 gastric carcinoma patients (relative risk 2.11). Conventional prognostic factors along with the type of organs invaded by the carcinoma had no impact on prognosis. CONCLUSIONS: Patients with T4 gastric carcinoma might be benefited from aggressive surgery with a curative intent. Whenever possible, splenectomy should be done along with invaded organ resection.

Esophageal resection in elderly esophageal carcinoma patients: improvement in postoperative complications.

BACKGROUND: Advanced age is considered to be a relative contraindication for radical esophagectomy with a three-field lymph node dissection. METHODS: Preoperative risks, postoperative morbidity and mortality, and long-term survival in 55 elderly patients (> or =70 years) who had undergone extensive esophagectomy for esophageal carcinoma were compared with those of 149 younger patients (<70 years). RESULTS: Elderly patients had worse preoperative cardiopulmonary function and had more frequent postoperative cardiopulmonary complications compared with younger patients (p < 0.05). The postoperative death rate was not statistically different between the elderly (10.9%) and younger groups (5.4%). When the study period was divided into an early and a late phase, the postoperative death rate dropped significantly (p < 0.05) in recent years (1.4%) when compared with the previous era (10.0%). The overall survival rates were not different between elderly and younger patients. CONCLUSIONS: Preoperative cardiopulmonary risk factors and postoperative complications after esophagectomy were more frequently noticed in elderly patients than in younger patients. A dramatic improvement in postoperative death was noticed in recent years. The long-term survival of elderly patients after extended esophagectomy was almost similar to that in younger patients.

Clinicopathologic factors correlated with number of metastatic lymph nodes in oesophageal cancer.

BACKGROUND: The number of metastatic lymph nodes is applied to the staging system of gastric cancer and colorectal cancer. However, it has not been evaluated in oesophageal cancer. PATIENTS AND METHODS: Of 258 patients with primary squamous cell carcinoma of the thoracic oesophagus between February 1981 and December 1999, 160 underwent three-field oesophagectomy with a curative intent. Clinicopathologic characteristics of those 160 patients were retrospectively investigated according to the number of metastatic lymph nodes. RESULTS: Seventy-eight patients had no lymph node metastases and 82 (51.3%) had lymph node metastases; 51 [31.9%)] had between 1 and 4 positive lymph nodes, and 31 (19.4%) had > or =5. The number of metastatic lymph nodes was significantly correlated with tumour size, macroscopic classification, histological differentiation, pT, pN, and vessel invasions. Multivariate analysis showed that lymph vessel invasion (relative risk 12.6), histological differentiation (relative risk 4.2), and tumour size (relative risk 3.8) were independent factors correlated with number of metastatic lymph nodes. The number of metastatic lymph nodes was also well correlated with the Japanese nodal level and TNM stage, respectively (p<0.001). The 5-year disease-specific survival rate according to the number of positive lymph nodes was 90% for patients without lymph node metastases, 52.2% with 1-4, and 28.9% with > or =5, respectively, p<0. 0001; 0 vs 1-4, p<0.05; 1-4 vs > or =5). CONCLUSION: The number of positive lymph nodes is well correlated with tumour progression and provides a useful prognostic indicator after oesophagectomy for oesophageal cancer.

Esophageal cancer with distant lymph node metastasis: prognostic significance of metastatic lymph node ratio.

The cervical and celiac lymph node metastases are defined as distant metastasis (Mlym) from thoracic esophageal carcinoma by TNM (primary tumor, regional lymph nodes, and distant metastasis) classification. The prognostic factors, however, of such distant node metastases are not fully understood. Of 85 patients with node-positive thoracic esophageal carcinoma who were treated with the same modalities of treatment, 31 (37%) had Mlym. Prognostic factors for long-term survival were analyzed by univariate and multivariate analyzes. Three patients are alive and free of cancer, and two patients survived over 5 years. Fifteen patients died of recurrent esophageal cancer and 11 patients succumbed to causes unrelated to esophageal cancer. Two patients with a single Mlym died without recurrence of esophageal cancer at 1.4 years and after more than 5 years, respectively. The 1-, 2-, 3-, and 5-year overall survival rates of all 31 patients were 64.5%, 24.8%, 17.0%, and 12.8%, respectively. The factors influencing survival rate were depth of invasion (pT1,2 vs. pT3,4) and metastatic lymph node ratio (< or =0.104 vs. > or =0.105). The survival rates were not influenced by number of lymph node metastasis, number of Mlym, or by metastatic lymph node ratio of Mlym. Among those two significant variables verified by univariate analysis, independent prognostic factor for survival determined by multivariate analysis was the metastatic lymph node ratio (risk ratio = 3.4, p = 0.0345). The results of this study indicate that a significant number of patients can be cured of esophageal carcinoma by extensive resection along with extended lymph node dissection even when the disease metastasizes to distant nodes.

Esophageal cancer with cirrhosis of the liver: results of esophagectomy in 18 consecutive patients.

BACKGROUND: Patients with cirrhosis of the liver sometimes are candidates for esophagectomy with extensive lymphadenectomy. MATERIALS AND METHODS: Of 271 patients with primary esophageal carcinoma, 19 patients (7.0%) had pathologically proven cirrhosis of the liver. Among those, 18 patients underwent esophagectomy with extensive lymph node dissection. Clinicopathologic characteristics of these 18 patients were retrospectively investigated. RESULTS: Pathological T stages were pT1 in 3 patients, pT2 in 9 patients, pT3 in 2 patients, and pT4 in 4 patients. Hepatitis C virus antibody was positive in 1 patient, and 14 patients were alcoholics. Three patients had cryptogenic cirrhosis. Seven patients were classified as Child-Turcotte B and 11 were Child-Turcotte A. Three patients had ICG-R 15 over 30%. Fifteen patients (83.3%) developed a total of 35 postoperative complications. Three patients currently are alive without recurrence. Fifteen patients have died: 7 from cancer recurrence; 5 of causes unrelated to esophageal cancer; and 3 of operative death (operative mortality: 16.7% in 18 cirrhotic patients vs. 5.7% in 227 non-cirrhotic patients; P = .102). The 1- and 3-year survival rates for 18 resected cirrhotic patients were 50% and 21%, respectively, and those for 227 resected non-cirrhotic patients were 67% and 42%, respectively (P = .051). When operative deaths were excluded from the analysis, the 1- and 3-year survival rates for 15 cirrhotic patients were 60% and 25%, respectively, whereas those for 214 non-cirrhotic patients were 68% and 43%, respectively (P = .271). CONCLUSION: Although cirrhosis has a high morbidity and mortality rate, Child-Turcotte A and B cirrhosis may not contraindicate curative esophagectomy for esophageal carcinoma. However, these patients need meticulous perioperative care to avoid postoperative complications.

Prognostic significance of Fas and Fas ligand system-associated apoptosis in gastric cancer.

BACKGROUND: Previous studies indicate that gastric carcinomas express Fas ligand and down-regulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated. METHODS: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method. RESULTS: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD8+ cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients' age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD8+ cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors. CONCLUSIONS: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD8 + cells.

A tailored perioperative blood transfusion might avoid undue recurrences in gastric carcinoma patients.

In a large retrospective study, the prognostic significance of blood transfusion (BT) and type of blood product transfused were searched in 640 curatively resected gastric carcinoma patients. Out of 640 patients, 222 (34.7%) received BT and the incidence of BT was reduced from 45% in the early period to 21% in the most recent period. The five-year disease-free survival was significantly (P < 0.0001) worse in the transfused group and BT became an independent prognosticator (P = 0.0061) in the multivariate analysis. Patients transfused with only packed red blood cells (PRBC) had significantly (P = 0.0258) better survival than those transfused with other types of blood products. In conclusion, BT was found to be an independent prognosticator in gastric carcinoma patients after curative resection. A tailored transfusion with PRBC, when indicated, might be the choice for better survival than whole blood or other blood products.

Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients.

The role of cyclooxygenase-2 (COX-2) in tumor neovascularization of human colorectal carcinoma is yet to be delineated. One hundred colorectal carcinoma specimens were evaluated for COX-2 expression and CD34-stained microvessel density (MVD) by immunohistochemical methods. The relationships between COX-2 expression and clinicopathological feature of the patients, MVD, and survival time were analyzed. Increased COX-2 expression was significantly correlated with pathologically unfavorable findings such as tumor size (> 3.0 cm), tumor differentiation (poor, moderate > well differentiated), number of metastatic lymph nodes (24), and Dukes' stage (Dukes' B, C, and D). Larger number of microvessels congregated around the COX-2-expressing area, and the Spearman rank correlation test showed a strong correlation between COX-2 expression and tumor MVD (P < 0.0001). Patients with COX-2-positive tumors had a significantly (P = 0.037, by log-rank test) shorter survival time than those with negative tumors did. In the multivariate analysis, however, only Dukes' stage and number of metastatic lymph nodes remained as independent prognostic factors. Augmented tumor neovascularization may be one of the several effects of COX-2 responsible for poor prognosis in human colorectal carcinoma patients.

Spontaneous apoptosis in advanced esophageal carcinoma: its relation to Fas expression.

The prognostic importance of spontaneous apoptosis and its correlation with clinicopathological characteristics and Fas expression have yet to be delineated in esophageal carcinoma. Specimens from 65 patients with advanced squamous cell carcinoma of the esophagus were used for immunohistochemical evaluation of Fas, proliferating cell nuclear antigen, and apoptosis. The mean apoptotic index (AI) of 65 tumors was 1.38 +/- 0.99% (range, 0.10-4.49%). Thirty-nine (60.0%) patients had a high AI, and 26 (40.0%) patients had a low AI. Low AI was correlated with advanced tumor stage (P = 0.0197) and weak Fas expression (P = 0.0093). Patients with a low AI had significantly (P = 0.0095) worse survival than those with a high AI. However, by multivariate analysis, low AI alone was not an independent prognosticator. When combined with cellular proliferation index, AI became an independent prognostic factor (P = 0.0283) in this group of patients. Our results suggest that enhanced Fas expression is responsible for high AI in squamous cell carcinoma of the esophagus. High AI, combined with the cellular proliferation labeling index, could be an independent prognostic indicator.

Prognostic factors in node-negative squamous cell carcinoma of the thoracic esophagus.

BACKGROUND: Among several clinicopathological factors influencing the outcome of patients with esophageal carcinoma, the presence or absence of lymph node metastasis is the most important. Prognostic indicators, however, in patients without lymph node involvement have not been fully understood. MATERIALS AND METHODS: Out of 247 patients with primary squamous cell carcinoma of the thoracic esophagus between February 1981 and December 1998, 154 patients (62.3%) underwent esophagectomy with curative intent; 78 patients (50.6%) had no lymph node metastasis. Clinicopathological characteristics of those node-negative 78 patients were investigated. RESULTS: Pathological tumor stages (pT) were pT1 in 44 patients, pT2 in 24 patients, pT3 in 9 patients, and pT4 in one patient. Forty-six patients are alive free of cancer and another one with pT2N0 tumor is alive with recurrence. Four patients died of recurrence; one in pT1 and three in pT3. The remaining 27 patients died of miscellaneous causes other than esophageal cancer. The 1-, 3-, 5-, and 10-year overall survival rates of all 78 patients including in-hospital mortality were 86.3%, 73%, 66.5%, and 34.6%, respectively. The 3- and 5-year survival rates were 75.4% and 67.7% for those with pT1, T2 tumor (n = 68) and 57.1% and 57.1% for those with pT3, T4 tumor (n = 10) (p = 0.0151). The factors influencing overall survival rate were patient age (< 65 vs. > or = 65), depth of invasion (pT1,T2 vs. pT3, T4), time of operation (< or = 420 min vs. > 420 min), and estimated blood loss (< or = 810 ml vs. > 810 ml). More elderly patients died of unrelated causes to esophageal cancer than younger patients. Among those four variables, the patient age (p = 0.0114) and depth of invasion (p = 0.0443) were independent prognosticators for survival determined by multivariate analysis. CONCLUSION: For follow-up of elderly patients with node-negative esophageal cancer, evaluation of medical problems is more important than detection of recurrence. pT2N0 stage tumors should be considered a group with an excellent prognosis like pT1N0 tumors.