Concurrent expression of angiogenic growth factors and neovascularization during tumourigenesis in colorectal carcinoma patients.

Details of concurrent expression of angiogenic growth factors (AGFs) and microvessel density (MVD) in human colorectal adenomas and carcinomas remain obscure. Eighty lesions, 20 each from colorectal adenoma, Tis, T1 and T2 cancers were evaluated immunohistochemically for basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (dThdPase) and MVD. MVD (p = 0.0001) and bFGF expression (p = 0.0001) increased in the order of adenoma, Tis, T1 and T2 cancers. VEGF expression was same in adenomas and cancers while dThdPase was weak in adenomas but strongly expressed in invasive carcinomas ( > T1). MVD had positive correlation with tumour size in small (< or = 4 cm) colorectal cancers. Concurrent expression of AGFs was noticed in invasive carcinomas. bFGF seems to be the strongest among the three AGFs expressed during colorectal carcinogenesis and had a significant correlation with tumour MVD. Concurrent expression of multiple AGFs is a crucial step in the transition from non-invasive to invasive carcinoma.

Enhanced apoptosis and transforming growth factor-beta1 expression in colorectal adenomas and carcinomas after Sulindac therapy.

PURPOSE: We tried to elucidate the effects of sulindac on human colorectal carcinoma. METHODS: Sulindac (300 mg/day) was administered for two weeks before operation to 33 patients with sporadic colorectal carcinoma (Sulindac Group). Resected specimens were used to detect apoptosis by terminal dUTP nick end labeling and transforming growth factor (TGF)-beta1 expression by immunohistochemistry. The results were compared with those from the historical Control Group. Twenty-nine available preoperative biopsies taken from carcinomas before sulindac prescription and 22 concurrent colorectal adenomas (9 and 13 in Sulindac and Control Groups, respectively) in the resected specimen were also examined regarding TGF-beta1 expression. RESULTS: In the resected carcinomas and adenomas, more frequent apoptosis and higher TGF-beta1 scores were observed in the Sulindac Group than in the Control Group. Overexpression of TGF-beta1 and apoptosis occurred in the same region in adenomas but not in carcinomas. A positive correlation between TGF-beta1 scores and apoptotic frequency was found in adenomas (P = 0.01, rho = 0.91) but not in carcinomas (P = 0.89, rho = 0.03). CONCLUSION: We conclude that sulindac induces apoptosis in human colorectal carcinomas as well as in adenomas. Also, one of the antineoplastic effects of sulindac might be mediated by upregulating TGF-beta1 expression, particularly in colorectal adenomas.

Sulindac inhibits growth of rat colon carcinoma by inducing apoptosis.

Sulindac possesses an inhibitory effect on colorectal cancer development. Rat colon cancer cells, ACL-15, inoculated subcutaneously in F344 rats were used. Sulindac was administered at 8 mg/kg twice daily for 7 consecutive days. Sulindac group and control group were compared regarding tumor volume and body weight. At sacrifice, the tumors were collected and examined for tumor-infiltrating lymphocytes, apoptotic index, and microvessel density. The tumor volume in the sulindac group was significantly smaller than that in the control group. Body weight, microvessel density, and tumor-infiltrating lymphocyte score were not significantly different between the two groups. The apoptotic index was significantly higher in the sulindac group than in the control group. Sulindac inhibited tumor growth by inducing apoptosis. These findings may be helpful in designing new treatment strategies in colorectal cancer patients.

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.

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.

Body mass index determines the success of lymph node dissection and predicts the outcome of gastric carcinoma patients.

We tried to determine the role of the body mass index (BMI) on the extent of lymph node dissection in gastric cancer surgery. Seven hundred and eighty-seven patients with gastric carcinoma were reviewed. Ninety-two (11%) patients exceeded the upper limit of the optimum BMI. Significantly fewer lymph nodes were removed following D2 (p = 0.002) and >/=D3 (p = 0.023) dissections, and the lymph node ratio was significantly (p = 0.0383) higher in overweight patients. The recurrence-free survival was significantly (p = 0.0297) shorter in T2/T3 cases with high BMI, and BMI (relative risk 1.85) became an independent prognostic factor in multivariate analysis. Higher BMI hampers regional lymph node dissection in gastric cancer patients and became an independent predictor of disease recurrences in T2/T3 gastric cancers.

Impact of screening survey of gastric cancer on clinicopathological features and survival: retrospective study at a single institution.

BACKGROUND: Detection of gastric cancer in an early stage is important to improve the prognosis of patients with gastric cancer. This study compared the clinicopathologic characteristics and surgical results in patients with asymptomatic gastric cancer detected by a screening program with those of patients with symptomatic cancer. The efficacy of 2 screening methods (barium meal and endoscopy) was also compared. METHODS: The subjects included 196 patients with asymptomatic gastric cancer detected by screening (screening group) and 612 patients with symptomatic gastric cancer (nonscreening group) treated from 1979 to 1997. The screening group was subdivided into the barium meal study group (n = 150) and the endoscopic study group (n = 46). RESULTS: The incidences of early gastric cancer and 5-year survival rates between the screening and nonscreening groups were 77% versus 29% (P <.0001) and 81% versus 44% (P <.0001), respectively. The endoscopic study appeared to be able to detect smaller gastric cancer in an earlier stage compared with the barium meal study, although no statistical differences in survival rate were noted between these 2 screening methods. CONCLUSIONS: Screening plays an important role in detecting gastric cancer in an early stage and in potentially reducing death attributable to gastric cancer. Endoscopic screening is recommended as the best screening method.

Gastric resection in the aged (> or = 80 years) with gastric carcinoma: a multivariate analysis of prognostic factors.

BACKGROUND: The incidence of gastric neoplasm is increasing in the elderly population. Therefore, a rational method of treatment for gastric cancer in the elderly should be constituted to improve the survival. The purpose of the present study was to clarify whether the patient's age is an independent prognostic factor and to determine clinicopathological characteristics in the elderly. METHODS: Curative resection of gastric cancer was carried out on 601 patients who were 40 years or older. They were divided into the following two groups: younger patients (between 40 and 79 years old) and elderly patients (80 years or older). The clinicopathologic features of these patients were reviewed retrospectively and multivariate analysis was carried out. RESULTS: The distinguishing features of gastric cancer in the elderly patients were intestinal and mixed types of cancer, distal third stomach dominance in the tumour location, advanced stage of disease, and a low rate of extensive lymph node dissection (D3 or more). Regarding the recurrence site, the liver was the dominant site in the elderly group (25.3% in the younger group vs 54.5% in the elderly group). The 10-year disease-free survival rate of the elderly group was 53.2%, which was significantly worse than that (79.9%) of the younger patients (P = 0.0004). In multivariate analysis, an age of > or = 80 years is an independent prognostic factor, as well as stage, depth of tumour invasion, lymph node metastasis, scirrhous carcinoma, and blood transfusion. CONCLUSIONS: Results indicate that gastric cancer in elderly patients has a poorer prognosis than that in younger patients.

Long-term survival of transmural advanced gastric carcinoma following curative resection: multivariate analysis of prognostic factors.

Patients with transmural (T2N0-T3N2) advanced gastric carcinoma comprise the largest group with uncertain outcome. These patients must be stratified according to the prognostic variables so the high risk group can be precisely identified. A total of 152 patients with transmural advanced gastric carcinomas were uniformly treated with a curative intent between 1979 and 1989 with at least a 7-year follow-up. Results and prognostic factors of long-term survival were analyzed by univariate and multivariate analyses. Seventy-five (49%) patients with advanced gastric carcinoma survived more than 7 years, which indicates the curative nature of surgery for gastric carcinoma. Seventeen variables were evaluated by univariate analysis. In the multivariate analysis, patient's age [>70 years, relative risk (RR) 2.4)], intraoperative blood loss (>500 ml, RR 1.7), blood vessel invasion (RR 2.3), ratio of invaded dissected lymph nodes (>0.2, RR 3.0), and tumors penetrating the serosa (RR 3.9) were the independent prognostic variables. The results of this study indicate that extensive lymphadenectomy and minimal intraoperative blood loss might be helpful for improving patient survival following a curative resection. Patients with vessel invasion, serosal involvement, and those >70 years of age should be considered at high risk and require appropriate adjuvant therapy to prolong survival.

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.

An evaluation of malignancy and prognostic factors based on mode of lymph node metastasis in esophageal carcinoma.

This study was conducted to evaluate lymph node metastasis as a key prognostic factor in esophageal cancer. Metastatic lesions in lymph nodes were grouped by histological morphology as intracapsular or extracapsular, and the significance of lymph node metastasis was evaluated by relating metastatic lesions to clinical pathologic factors and patient prognosis. In our hospital, 46 of 81 patients who underwent resection of esophageal cancer developed lymph node metastasis. These 46 patients were enrolled in a study analyzing the relationship between the metastatic mode and the clinicopathological factors. The frequency of extracapsular metastasis was significantly high in patients with a profound depth of cancer, three or more metastases, distant metastasis (n3 and n4), or severe lymphatic invasion. The prognosis was significantly worse in patients with extracapsular metastasis, and this tendency was also seen even in patients with three or more metastases, limited metastasis (n1 and n2), or mild lymphatic invasion (ly0 and ly1). These findings suggest that the metastatic mode reflects the degree of esophageal cancer progression and is an important prognostic factor.

Prognostic factors after extended esophagectomy for squamous cell carcinoma of the thoracic esophagus.

BACKGROUNDS AND OBJECTIVES: In Japan, extended esophagectomy with extensive lymphadenectomy has become the standard surgical procedure for carcinoma of the thoracic esophagus. Although mortality and morbidity rates after such extensive esophagectomy have been acceptable, the long-term outcomes are not necessarily satisfactory. METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between June 1981 and March 1998, 143 patients (60.9%) underwent extended esophagectomy with extensive lymphadenectomy. To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days after operation were excluded. Thus, clinicopathological characteristics and prognostic factors of 129 patients were retrospectively investigated. RESULTS: Sixty-three patients were alive and free of cancer. Sixty-six patients died: 37 of recurrence of the esophageal cancer and 29 of other causes. The 1-, 3-, 5-, and 10-year overall survival rates in the 129 patients were 78.8%, 53.5%, 45.8%, and 30.9%, respectively, and the disease-specific survival rates were 85.7%, 69.1%, 67.9%, and 56.2%, respectively. The factors influencing the disease-specific survival rate were tumor location (upper third vs. non-upper third), Borrmann classification (0, 1 vs. 2, 3), size of tumor (3.0 cm), depth of invasion (T1, 2 vs. T3, 4), number of lymph node metastases (0 or 1 vs. >/=2), time of operation (420 min), amount of blood transfused (/=3 U), lymph vessel invasion (marked vs. not marked), and blood vessel invasion (marked vs. not marked). Among those significant variables, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastases (P < 0.001), amount of blood transfusions (P = 0.0016), and tumor location (P = 0.0382). CONCLUSIONS: Patients with a single metastatic node after extended esophagectomy should be considered to have excellent prognosis, like patients with pN0 tumors. Patients with multiple involved nodes should receive aggressive postoperative adjuvant treatments. Reduced blood loss during extended esophagectomy and minimal blood transfusions might improve the outcome of curative esophageal resections.

Prognostic significance of Fas and Fas ligand expressions in human esophageal cancer.

Esophageal carcinomas have recently been shown to express Fas ligand (FasL) and down-regulate Fas to escape from host immune surveillance. However, the prognostic importance of Fas/FasL and their correlation with clinicopathological characteristics are yet to be delineated in this highly malignant carcinoma. Specimens from 106 esophageal squamous cell carcinoma patients were used for immunohistochemical evaluation of Fas, FasL, and CD8 expressions. Fifty-two (49%) and 34 (32%) patients were positive for FasL and Fas, respectively. There were no associations between FasL expression and clinicopathological characteristics except lymph vessel invasion. Strong FasL expression correlated with significant (P = 0.0011) decrease in tumor nest CD8+ cells. However, neither FasL nor CD8+ had any impact on patient survival. Strong Fas expression was correlated with depth of invasion (40.3% in pT1,T2 versus 20.5% in pT3,T4; P = 0.0308), histological differentiation (45.7% in well versus 25.4% in nonwell; P = 0.0347), and lymph node metastasis (22.6% in positive versus 45.5% in negative; P = 0.0129). Fas expression was one of the independent favorable prognosticators for patients' survival (risk ratio, 3.26; P = 0.0103) in esophageal SCC. Fas expression was an independent prognosticator for recurrence-free survival, whereas FasL expression did not influence the survival in esophageal squamous cell carcinoma. Down-regulation of tumor Fas may be the hallmark of immune privilege for the tumor, thus causing the patients' poorer outcome. Tumor FasL may counterattack the host immune cells to such an extent that the prognosis is not affected.

Clinicopathological features of early gastric cancer: results of 100 cases from a rural general hospital.

OBJECTIVE: To evaluate 100 patients with early gastric cancer from the point of view of early detection, clinicopathological variables, and long term results. DESIGN: Retrospective study. SETTING: Rural general hospital, Japan. SUBJECTS: 100 patients with early gastric cancer (confined to the epithelium, lamina propria, or submucosa) out of a total of 197 who had gastric cancers resected for cure between May 1986 and April 1996. INTERVENTIONS: Subtotal gastrectomy (n = 87), total gastrectomy (n = 8), proximal gastrectomy (n = 2), and local wedge resection (n = 3). MAIN OUTCOME MEASURES: Histopathological features and outcome. RESULTS: The mean annual incidence of early gastric cancer was 51% (range 35%-70%). 16/59 patients with mucosal cancer (37%) and 18/41 with submucosal cancer (44%) presented with symptoms of the disease. The diagnosis was made in 62 by endoscopy, and in only 2 by upper gastrointestinal radiographic examination. None of the 59 with mucosal cancer had lymphatic invasion, and only 1 had a lymph node metastasis. Among the 41 with submucosal cancer, however, 15 had lymphatic invasion (37%), 13 had venous invasion (32%), and 2 had lymph node metastases (5%). 83 patients were alive with no sign of recurrence at the time of writing (median follow up 62 months, range 12-136). One patient with a tumour that produced alpha-fetoprotein died of hepatic metastases 23 months after subtotal gastrectomy. 9 patients developed second cancers, and 6 died of these with no signs of recurrence of early gastric cancer. The overall 5 and 10 year survival rates were 82% and 66%, and the corresponding disease-specific survival rates for 85 patients were both 98%. CONCLUSIONS: Excellent long term results can be achieved in the treatment of early gastric cancer, even in a non-specialist centre. Patients with early gastric cancer should have their alpha-fetoprotein concentration measured, and be examined for the presence of other malignant disease both before and after treatment of the gastric cancer.

Antiangiogenic therapy of human esophageal cancers with thalidomide in nude mice.

BACKGROUND: Thalidomide (alpha-N-phthalimidoglutarimide) is attracting new attention because of its antiangiogenic effect in corneal neovascularization models. However, the effect of this agent on esophageal carcinoma is yet to be established. METHODS: The human esophageal squamous cell carcinoma strains ES63 and ES80 implanted subcutaneously in nude mice were used to evaluate the antiangiogenic effect of thalidomide (200 mg/kg/d) after daily gavage or intraperitoneal administration. Tumor size was measured, and assessment of microvessel density was performed histochemically with Griffonia simplicifolia lectin I. Characterizations of angiogenic growth factors, vascular endothelial growth factor, basic fibroblast growth factor, and thymidine phosphorylase in ES63 and ES80 tumors were done by immunohistochemical staining and reverse transcription-polymerase chain reaction. RESULTS: ES63 strongly expressed 3 angiogenic factors, but ES80 showed moderate expression of thymidine phosphorylase and only weak or no expression of vascular endothelial grown factor and basic fibroblast growth factor at protein and messenger RNA levels. In ES63 intraperitoneal injection of thalidomide produced significant (P < .05) inhibition of tumor growth, but there was no effect after gastric gavage. Also, a significantly (P < .0005) lower microvessel density was encountered in the intraperitoneal thalidomide group. However, in the ES80 tumor strain thalidomide had no antiangiogenic effect after either intraperitoneal or oral administration. CONCLUSIONS: These data indicate that thalidomide exerts an antiangiogenic effect on solid tumor after intraperitoneal administration. Thalidomide might be one of the hopeful antiangiogenic drugs for solid tumors.

Prognostic significance of perioperative blood transfusions in resectable thoracic esophageal cancer.

OBJECTIVE: The perioperative blood transfusions have been associated with tumor recurrence and decreased survival in various types of alimentary tract cancer. There exist, however, contradictory studies showing no relationship between blood transfusions and survival. For patients with esophageal cancer, only one report suggested that blood transfusions did not by itself decrease the chance of cure after esophagectomy. METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between December 1979 and March 1998, 143 patients (60.9%) underwent esophagectomy with curative intent (RO). To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days during the hospital stay were excluded. Thus, clinicopathological characteristics and prognostic factors were retrospectively investigated between patients with no or few transfusions (< or = 2 units) (n = 58), and much transfused patients (> or = 3 units) (n = 71). RESULTS: Sixty-three patients are alive and free of cancer, and 66 patients are dead. A total of 98 patients (76%) received blood transfusions, whereas 31 patients (24%) had no transfusion. The amount of blood transfused was 1 or 2 units in 27 patients (27.6%), 3 or 4 units in 33 (33.7%), 5 or 6 units in 20 (20.4%), and > or = 7 units in 18 (18.4%). The 5-yr survival rate for patients with no or few transfusions was 69%, whereas that for much transfused patients was 31.7% (p < 0.0001). The much transfused patients had more prominent ulcerative tumor, longer time of operation, more estimated blood loss, and more marked blood vessel invasion than the group with no or few transfusions. The factors influencing survival rate were tumor location, Borrmann classification, size of tumor, depth of invasion, number of lymph node metastases, time of operation, amount of blood transfusions, lymph vessel invasion, and blood vessel invasion. Among those nine significant variables verified by univariate analysis, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastasis (0 or 1 vs > or = 2, p < 0.0001), amount of blood transfusions (< or = 2 units vs > or = 3 units, p < 0.0001), and blood vessel invasion (marked vs non-marked, p = 0.0207). CONCLUSIONS: There is an association between high amount of blood transfusions and decreased survival for patients with resectable esophageal cancer. To improve the prognosis, surgeons must be careful to reduce blood loss during esophagectomy with extensive lymph node dissection and subsequently must minimize blood transfusions.

nm23 in the primary and metastatic sites of gastric carcinoma. Relation to AFP-producing carcinoma.

Tumor metastasis is the major cause of treatment failure and death in cancer patients. The present study was designed to extrapolate the association of nm23 expression with acquisition of metastatic potential of gastric carcinoma with special reference to the alpha-fetoprotein-producing gastric carcinoma (APGC). The primary tumor with surrounding normal mucosa and metastatic lymph nodes of 30 patients with APGC and 29 randomly selected matched controls of non-AFP gastric carcinoma (NAGC) were immunostained for nm23 and an image analyzer system was used for quantitative evaluation. Overexpression of nm23 was noted in 71% (42/59) of the primary tumors and 18% (10/55) of the metastatic tumors and there was no difference between the APGC and NAGC groups. The overexpression of nm23 in the primary tumors correlated with tumor invasion, metastasis and progression in all cases and similar results were obtained in the APGC and NAGC groups except for the tumor stage which was insignificant in the APGC group. The patient survival was adversely affected by the overexpression of nm23 in the primary sites and downregulation in the metastatic sites in all cases but lost their significance in the multivariate analysis. However, nm23 status did not affect patient survival in the APGC group.

Prognostic factors in T1 and T2 squamous cell carcinoma of the thoracic esophagus.

BACKGROUND: Prognostic indicators in patients with T2 tumor have not been fully understood. OBJECTIVE: To clarify the clinicopathologic characteristics and long-term results of T1 and T2 squamous cell carcinomas of the thoracic esophagus. DESIGN: Consecutive case series. SETTING: Department of surgery in a university hospital. PATIENTS: Of 234 patients with primary squamous cell carcinoma of the thoracic esophagus, 142 patients underwent esophagectomy with curative intent: 97 patients had pT1 and pT2 tumors. INTERVENTIONS: Investigated were clinicopathologic characteristics of 65 of 97 patients with pT1 and pT2 tumors; excluded were 7 patients who died of postoperative complications and another 25 patients who died of causes other than esophageal cancer. MAIN OUTCOME MEASURES: Clinicopathologic characteristics and long-term results. RESULTS: Pathologic tumor stages were pT1 N0 in 23 patients, pT1 N(+) in 7 patients, pT2 N0 in 15 patients, and pT2 N(+) in 20 patients. Fifty patients are alive and free of cancer and 15 patients died of tumor recurrence (1 patient with pT1 N0 tumor, 1 patient with pT1 N[+][+] tumor, 1 patient with pT2 N0 tumor, and 12 patients with pT2 N[+] tumor). The sites of metastatic nodes in 6 survivors with pT1 N(+) tumor were a solitary perigastric node in 4 patients, a solitary mediastinal node in 1 patient, and 2 mediastinal nodes in 1 patient. The 5-year survival rates of patients with pT1 N0, pT1 N(+), and pT2 N0 tumors all exceeded 85%, and the rate of those with pT2 N(+) tumor was 33.9% (pT2 N[+] vs. others: pT1 N0, pT1 N[+], and pT2 N0; P = .003). The factors affecting survival rate by univariate analysis were Borrmann classification (0, 1 vs. 2, 3, 4), tumor size (<4.0 vs. > or =4.0 cm), combined T, N factor (pT2 N[+] vs. others), time of operation (< or =420 vs. >420 minutes), estimated blood loss (<1000 vs. > or =1000 mL), and lymph vessel invasion (marked vs. not marked). Stage pT2 N(+) tumor became a single independent prognostic factor for survival as determined by multivariate analysis (pT2 N[+] vs. others; P = .008). CONCLUSIONS: Stage pT1 N(+) tumors with a few diseased nodes and pT2 N0 tumors are considered to be a group with an excellent prognosis, similar to pT1 N0 tumors. Patients with pT2 N(+) diseases had worse prognoses and thus should have meticulous lymph node dissection and extensive adjuvant therapy.

Serum carcinoembryonic antigen as a prognostic factor in resectable gastric cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) has been widely accepted as a tumor marker useful in the diagnosis and management of colorectal cancer. When CEA levels are positive in gastric cancer patients, they could be useful prognostic indicators. However, the value of CEA as a tumor marker for gastric cancer remains a matter of controversy. STUDY DESIGN: We measured preoperative serum CEA levels in 196 patients with resectable gastric cancer between May 1986 and April 1996 and then evaluated the correlation between serum CEA levels, clinicopathologic features, and prognostic information. RESULTS: Serum levels of CEA were above the normal range in 29 of 196 (14.8%) surgically resected patients (range, 5.2-570 ng/mL). Among 100 early gastric cancers confined to the submucosal layer, only 7 patients (7.0%) had positive CEA levels, but among 96 advanced cancers, 22 patients (22.9%) had high CEA levels. The CEA positive patients had more macroscopically infiltrative tumors, a more prominent serosal invasion, more frequent lymph nodes involvement, and a more advanced stage than did the CEA negative patients. The 3- and 5-year cumulative disease-specific survival rates of patients positive for serum CEA were 39.6% and 31.7%, respectively; these rates for patients negative for CEA were 83.0% and 77.3%, respectively (p < 0.0001 for comparison of survival curves). In various clinicopathologic parameters, nine parameters (tumor size, macroscopic type, type and time of operation, Laurén classification, depth of invasion, lymph node involvement, CEA, alpha-fetoprotein [AFP], and carbohydrate antigen [CA] 19-9) showed statistically significant differences in the cumulative survival rates. Of these nine parameters, independent prognostic factors by multivariate analysis were depth of invasion (T1, 2 versus T3, 4, p < 0.0001), serum CEA levels (negative versus positive, p = 0.0003), and lymph node metastasis (negative versus positive, p = 0.0005). CONCLUSIONS: Preoperative serum CEA levels provide a predictive value in determining tumor stage and prognostic information for patients with potentially resectable gastric cancer during the preoperative period.