Clinical TNM staging for esophageal, gastric, and colorectal cancers in the era of neoadjuvant therapy: A systematic review of the literature.

AIM: Clinical staging is vital for selecting appropriate candidates and designing neoadjuvant treatment strategies for advanced tumors. The aim of this review was to evaluate diagnostic abilities of clinical TNM staging for gastrointestinal, gastrointestinal cancers. METHODS: We conducted a systematic review of recent publications to evaluate the accuracy of diagnostic modalities on gastrointestinal cancers. A systematic literature search was performed in PubMed/MEDLINE using the keywords "TNM staging," "T4 staging," "distant metastases," "esophageal cancer," "gastric cancer," and "colorectal cancer," and the search terms used in Cochrane Reviews between January 2005 to July 2020. Articles focusing on preoperative diagnosis of: (a) depth of invasion; (b) lymph node metastases; and (c) distant metastases were selected. RESULTS: After a full-text search, a final set of 55 studies (17 esophageal cancer studies, 26 gastric cancer studies, and 12 colorectal cancer studies) were used to evaluate the accuracy of clinical TNM staging. Positron emission tomography-computed tomography (PET-CT) and/or magnetic resonance imaging (MRI) were the best modalities to assess distant metastases. Fat and fiber mode of CT may be useful for T4 staging of esophageal cancer, CT was a partially reliable modality for lymph node staging in gastric cancer, and CT combined with MRI was the most reliable modality for liver metastases from colorectal cancer. CONCLUSION: The most reliable diagnostic modality differed among gastrointestinal cancers depending on the type of cancer. Therefore, we propose diagnostic algorithms for clinical staging for each type of cancer.

Preclinical assessment and pilot study using anti-CEA monoclonal antibody 1B2 for colorectal carcinoma imaging.

BACKGROUND/AIMS: Preclinical assessment of radio-labeled monoclonal antibodies is essential to the understanding of target-specific tumor localization. The purpose of this study is to prepare for fundamental evaluation of antibodies and to validate the clinical usefulness of the candidate considered useful for practice through preclinical assessment. METHODOLOGY: The immunoreactivity and affinity constant of three kinds of monoclonal antibody (1A4, 1B2, 4H11: CEA-specific) were evaluated with the method of cell binding assay. Tumor localization and biodisrtibution were performed in tumor-bearing athymic mice. Five patients of colorectal cancer underwent radioimmunodetection with 99mTc. Histological analysis was performed to evaluate the tumor localization of injected antibody. RESULTS: The immunoreactive fraction value of 1B2 is the highest than the other antibodies. The difference between the antibody affinities among three antibodies although were rather small. In an animal model, 1B2 obtained more highly tumor targeting and cleared more rapidly from the blood than the other two antibodies did. Pilot study using 1B2 was successful in all cases without background imaging. Visualization of tumor sites surgically removed revealed positive CEA and IgG immunostaining. CONCLUSION: The preparation for preclinical assessment of the characteristic parameters is practically valuable for clinical application of radiolabeled antibodies.

Surgical outcome of patients with thoracic esophageal cancer positive for cervical lymph nodes.

BACKGROUND/AIMS: Although cervical lymph nodes were classified as distant metastases in patients with thoracic esophageal cancer, not a few patients survive more than five-years. The purpose of this study was to predict patients with good prognosis among thoracic esophageal cancer patients with cervical node metastases. METHODOLOGY: From 1983 to 2002, 312 consecutive patients with thoracic esophageal squamous cell carcinoma underwent curative surgery with 3-field lymph node dissection (3FLD). A total of 88 (28%) of 312 patients were diagnosed with cervical lymph node metastases. Univariate and multivariate analyses were carried out to evaluate the impact of clinico-pathological factors on the survival of these patients. RESULTS: Overall five-year survival rate of 88 patients with cervical lymph node metastases was 26%. Univariate analysis revealed that following groups showed more than 40% overall five-years survival rate; female patients, patients with T1, T2 tumors and patients without thoracic node metastases. These variables were also independent good prognostic factors in multivariate analysis. CONCLUSIONS: Although cervical lymph node metastases was risk factors for worse survival, female patients, patients with T1, T2 tumors and patients without thoracic node metastases showed acceptable overall survival after 3FLD.

Evaluation of the hepatic blood flow increase in the cases with liver metastasis and prediction of patent cases of liver metastasis using dynamic CT.

BACKGROUND/AIMS: This study aimed to measure hepatic blood flow increase in cases with liver metastasis and to diagnose minimal metastasis which cannot be visualized by imaging modalities. METHODOLOGY: The evaluation of hepatic arterial flow increase was performed quantitatively by newly devised index ELR (early-late-ratio) using dynamic computed tomographic (CT) scanning with contrast media. RESULTS: The ratio of the cases with liver metastasis was significantly higher than that of normal liver control. It was revealed that the ratio was correlated with microvessel proliferation in the liver around the metastasis by examination of surgical specimen. Moreover, the patent group which proved to have metastasis within 6 months also had a significant higher ELR value. CONCLUSIONS: ELR not only was useful to evaluate hepatic blood flow increase in the cases with liver metastasis but also could be applied to predict the patent group with micrometastasis.

Location and clinical impact of solitary lymph node metastasis in patients with thoracic esophageal carcinoma.

BACKGROUND: The location and clinical impact of solitary lymph node metastasis from thoracic esophageal carcinoma have not been evaluated sufficiently. METHODS: A consecutive series of 91 patients with a solitary positive lymph node who underwent curative surgery for thoracic esophageal carcinoma was investigated. The prognostic impact was evaluated by univariate analysis and multivariate analysis using Cox's proportional hazards model. RESULTS: A total of 52 (57%) of the 91 patients showed a solitary positive node beyond the thorax. While 29% of the patients with an upper thoracic tumor showed a cervical node, 13% of the patients with a middle tumor and none of the patients with a lower tumor showed a cervical node. Tumor depth and venous invasion were found to be independent risk factors for poor survival. CONCLUSIONS: The solitary positive lymph nodes were broadly distributed depending on the tumor location and tumor depth. Tumor depth and venous invasion were risk factors for poor survival in these patients.

Prediction of lymph node status in patients with superficial esophageal carcinoma: analysis of 160 surgically resected cancers.

BACKGROUND: The ability to predict lymph node metastasis in cases of superficial esophageal carcinoma before surgery would allow the identification of specific patients who do not require additional surgical resection after endoscopic local resection. METHODS: From 1980 to 2002 a total of 160 patients with superficial esophageal carcinoma, Tis or T1 tumors, underwent subtotal esophagectomy with lymph node dissection. On the basis of clinicopathologic data the risk factors for lymph node metastases are discussed. RESULTS: Patients with tumors that showed submucosal invasion, a nonflat shape, and lymphatic invasion had a higher risk for lymph node metastasis than the other patients. Multivariate analysis showed that the tumor depth and the macroscopic shape of the tumor were independent risk factors for lymph node metastases. CONCLUSIONS: Esophagectomy with lymph node dissection is recommended for patients with submucosal cancer. Local tumor resection can be recommended for patients with mucosal cancer without lymphatic invasion.

Treatment response and prognosis of patients after recurrence of esophageal cancer.

BACKGROUND: Although radical operation and adjuvant chemoradiotherapy improve survival in patients with advanced esophageal cancer, more than half of these patients have recurrence. The aim of this study was to explore treatment responses and prognostic factors in patients with recurrent esophageal cancer. METHODS: The operative specimens from 258 patients undergoing radical esophagectomy with extended lymphadenectomy for esophageal squamous cell carcinoma between 1990 and 1999 were analyzed. Depth of tumor invasion, and the extent and location of lymph node metastases were determined. Postoperative recurrence was identified from positive findings on successive 3-month examinations of tumor markers, 6-month examinations of ultrasonography, and annual computed tomography. Of 258 patients, 95 had recurrence by the end of 2000 (mean follow-up was 22 months, range, 2-113). Of those 95 patients, 76 received nonsurgical treatment, 7 received operative intervention, and 12 received no treatment. Clinicopathologic features of recurrent tumors were analyzed to determine prognostic values. Serum anti-p53 antibodies (S-p53-Abs), serum C-reactive protein concentration (S-CRP), and albumin concentration were also analyzed. RESULTS: The main recurrent patterns were nodal (n = 45) and organ (n = 35). Of the nonsurgical treatment group, 47 patients received chemoradiotherapy; 17, chemotherapy; and 12, radiotherapy. Overall clinical response was observed in 26 of 76 patients (34%). Treatment response was significantly associated with the type of recurrence, history of perioperative adjuvant therapy, time of recurrence, number of recurrent tumors, albumin concentration, S-CRP, and S-p53-Abs. Multivariate analysis suggested that S-p53-Abs and S-CRP were independent prognostic factors. CONCLUSION: The status of S-p53-Abs and S-CRP may predict response and outcome of patients with recurrence of esophageal cancer after radical operation.

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.

Prognostic significance of serum p53 antibody in patients with esophageal squamous cell carcinoma.

BACKGROUND: The p53 protein overexpression that usually results from genetic alterations has been reported to induce serum antibodies against p53. There is little information about the clinicopathologic and prognostic significance of preoperative serum p53 antibody in patients with esophageal cancer. METHODS: A highly specific enzyme-linked immunosorbent assay was used to analyze serum p53 antibodies in 105 patients with esophageal squamous cell carcinoma. The cutoff level of 1.3 U/mL was used to indicate seropositive patients, and the cutoff level of 10 U/mL was used to identify high titer patients. At 3 months after surgery, seropositive patients were examined again. RESULTS: A total of 28 patients (26.7%) were positive for serum p53 antibodies. The patients who remained seropositive were more likely to develop tumor recurrence (P =.025). Seropositive patients had worse outcome than seronegative patients. The high titer group had significant association with advanced tumor stages and worse outcomes than the low titer group. High serum p53 antibody titer was an independent prognostic factor (P <.001). CONCLUSIONS: We found that serum p53 antibody was useful to detect esophageal cancer and to identify those with a high risk of tumor recurrence and a poor prognosis.

Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma.

BACKGROUND: Thrombocytosis in patients with cancer has been reported to be associated with increased expression of angiogenic factors and with a poor prognosis in some types of cancer. The aim of this study is to analyze the clinicopathologic significance and prognostic value of platelet counts in patients with esophageal cancer. STUDY DESIGN: Platelet counts were measured before surgery in 374 patients diagnosed between 1987 and 1999 with primary esophageal squamous cell carcinoma. We used the cut-off level of 293 x 10(9)/L (mean of 80 healthy controls +/- standard deviation) to define thrombocytosis. We analyzed the relationship between platelet counts, TNM factors, and white blood cell counts. Among 374 patients, the levels of C-reactive protein were analyzed in 170 patients and serum thymidine phosphorylase concentration was analyzed in 91 patients. The multivariate prognostic value of platelet counts, tumor size, and TNM factors were determined using Cox's proportional hazards model. RESULTS: Platelet counts were significantly increased in patients with large tumors (p < 0.001), deep tumors, nodal involvement, and distant metastasis in univariate analysis. C-reactive protein level, white blood cell count, and serum thymidine phosphorylase concentration were also significantly increased in patients analyzed with thrombocytosis in univariate analysis. Adjusting for tumor size and TNM factors, multivariate analysis indicated that thrombocytosis as defined in this study was an independent prognostic factor (hazard ratio = 1.52, 95% CI = 1.11 to 2.08, p = 0.009). CONCLUSIONS: A high platelet count is associated with tumor progression and poor survival in patients with esophageal carcinoma.

Prognostic significance of CYFRA 21-1 in patients with esophageal squamous cell carcinoma.

BACKGROUND: CYFRA 21-1 has been reported as a useful tumor marker for esophageal carcinoma, but little information was reported about the clinicopathologic importance of CYFRA 21-1. The aim of this study was to analyze the clinicopathologic and prognostic significance of preoperative CYFRA 21-1 in patients with esophageal squamous cell carcinoma. STUDY DESIGN: The CYFRA 21-1 levels were measured before surgery by enzyme-linked immunosorbent assays in 157 patients with primary esophageal squamous cell carcinomas using 3.5 ng/mL as the upper limit of normal. All patients underwent radical surgical procedures without any preoperative therapy. The association between the clinicopathologic factors assessed and the CYFRA 21-1 level was determined. The CYFRA 21-1 values were monitored after surgery in 45 available patients. The prognostic values were determined by multivariate analysis using Cox's proportional hazards model. RESULTS: Thirty-one of the 157 patients (19.7%) had high CYFRA 21-1 levels (> or =3.5 ng/mL). CYFRA 21-1 levels were significantly increased in patients with large tumors (> or =40 mm, p = 0.009), deep tumors (T2-T4, p = 0.003), and node-positive tumors (p = 0.003). CYFRA 21-1 levels significantly decreased after surgery (p < 0.001). A high CYFRA 21-1 level before surgery was an independent prognostic factor for survival (p = 0.043). CONCLUSIONS: A high CYFRA 21-1 level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Increased serum midkine concentration as a possible tumor marker in patients with superficial esophageal cancer.

Midkine, a heparin-binding growth factor, is expressed in numerous cancer tissues and is reportedly elevated in patients with various neoplasms. The aim of this study was to evaluate the clinicopathological significance of serum midkine concentration (S-MK) in patients with superficial esophageal squamous cell carcinoma (SCC). Pretreatment S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 60 patients with primary superficial esophageal squamous cell cancer (SESCC). All patients with SESCC underwent curative resection. The disease was staged according to TNM/UICC guidelines. Serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated in the same populations. S-MK in patients with SESCC (388+/-411 pg/ml) was significantly higher than in benign esophageal disease or healthy controls (183+/-73 and 154+/-76 pg/ml, respectively). Using the mean + 2 standard deviations of healthy control S-MK (300 pg/ml) as the cut-off level, 50% of patients with esophageal SESCC were deemed positive. This S-MK positivity rate for detecting SESCC was significantly higher than for other tumor markers. Thus, S-MK may be useful as a tumor marker to detect SESCC.

Long-term results after dissection of positive thoracic lymph nodes in patients with esophageal squamous cell carcinoma.

BACKGROUND: Although thoracic lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma (SCC) has been reported to be a negative risk factor for long-term survival, only a few studies have evaluated the clinicopathologic difference between the impact of metastasis to the paraesophageal lymph nodes and to the nonparaesophageal lymph nodes. The purpose of this study was to evaluate surgical outcome after the clearance of metastatic thoracic lymph nodes. METHODS: Retrospectively reviewed were 164 consecutive patients with thoracic esophageal SCC who had not had preoperative treatment and underwent surgery from 1980 to 2005 and were found to have thoracic lymph node metastases. Of these patients, 83 underwent surgery from 1980 to 1994 and 81 from 1995 to 2005. Univariate and multivariate analyses were performed to evaluate the impact of nonparaesophageal lymph node metastasis on survival. RESULTS: Univariate analysis revealed that T3/T4 tumors and the presence of nonparaesophageal node metastases were associated with only a 20% overall five-year survival rate. The overall five-year survival for the most recent period was significantly better than for the former period (42% vs. 13%, p<0.01). Based on a multivariate analysis of prognostic impact of each nonparaesophageal node, the presence of metastatic subcarinal and/or posterior mediastinal nodes was an independent risk factor for reduced survival. CONCLUSION: Surgical outcome for patients with thoracic esophageal cancer and metastatic thoracic lymph nodes has improved during the last 25 years. Although postoperative chemotherapy might improve survival, the presence of T3/T4 tumors and/or metastatic nonparaesophageal nodes were unfavorable factors for survival.

Surgical outcome after the clearance of abdominal metastatic lymph nodes in 138 patients with thoracic esophageal carcinoma.

BACKGROUND: Although abdominal lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma (SCC) has been reported to be a risk factor to reduce long-term survival, only a few studies have so far evaluated the clinicopathologic factors among this group of patients. The purpose of this study was to evaluate the patients' surgical outcome after the clearance of metastatic abdominal nodes. PATIENTS AND METHODS: From 1980 to 2002, 550 consecutive patients with thoracic esophageal SCC underwent surgery with an abdominal lymph node dissection. A total of 138 patients with abdominal lymph node metastases were curatively resected. Those patients, including 62 from 1980 to 1989 and 76 from 1990 to 2002, were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathologic factors on the survival of these patients. RESULTS: The overall 5-year survival rate of the 138 patients with abdominal lymph node metastases was 23%. A univariate analysis revealed that the following groups showed a greater than 30% overall 5-year survival rate: patients with T1 or T2 tumors, patients without thoracic node metastases, and those with poorly differentiated type tumors. Good prognostic factors based on a multivariate analysis were the most recent time period of surgery and 4 or fewer positive nodes. CONCLUSION: Among the patients with abdominal lymph node metastases, those with T1 or T2 tumors, patients without thoracic node metastases, and patients with 4 or fewer positive nodes showed an acceptable overall survival after a curative resection.

Impact of the number and extent of positive lymph nodes in 200 patients with thoracic esophageal squamous cell carcinoma after three-field lymph node dissection.

BACKGROUND: Subtotal esophagectomy with three-field lymph node dissection (3FLD) has been reported to improve survival in patients with thoracic esophageal squamous cell carcinoma (SCC). The purpose of this study was to evaluate the prognostic impact of the extent and number of positive lymph nodes for long-term survival of patients who underwent 3FLD. METHODS: From January 1983 to December 2002, a total of 200 patients with thoracic esophageal SCC underwent 3FLD without any neoadjuvant therapy. The prognostic impact of the extent and number of positive lymph nodes was evaluated by both univariate and multivariate analysis. RESULTS: The extent of positive nodes associated with a 5-year survival were as follows: none, 69%; one-field, 50%; two-field, 29%; and three-field, 11%. The number of positive nodes associated with 5-year survival were as follows: single node, 65%; two-nodes, 51%; and more than three-nodes, 20%. Among patients with cervical lymphatic spreading, patients with upper tumors showed significantly better survival than patients with lower tumors (P=0.036). Multivariate analysis indicated that number of positive nodes and the abdominal node status were independent prognostic factors among lymph node status. CONCLUSIONS: Together, number and extent of positive lymph nodes can be considered an independent predictor of a high risk of recurrence. Although cervical lymphatic spreading was risk factor for worse survival, patients with upper tumors may have survival benefit after cervical lymph node dissection.

The effects of carbon ion irradiation revealed by excised perforated intestines as a late morbidity for uterine cancer treatment.

PURPOSE: Clinical trials of carbon ion therapy have been performed due to the advantages of high-dose energy delivery with precise localization control to targeted organs and strong cell-killing activities to cancers. Perforated intestines as a late morbidity after carbon ion radiotherapy for uterine cancers were examined to reveal the biological characteristics of carbon ion for future applications for the treatment of gastrointestinal cancers. METHODS: Between June 1995 and December 2004, 94 patients with carcinoma of the uterine cervix or corpus were treated with carbon ion therapy. Among them, 9 patients (9.6%) developed major late gastrointestinal (GI) complications. Four out of 9 patients had intestinal perforations excised operatively at our institute. The postoperative clinical courses and histopathological findings of the excised intestine were investigated. RESULTS: Carbon ion irradiation severely damaged smooth muscle layers by coagulation necrosis as well as atrophy of the intestinal epithelium and middle-sized arterial thromboses of the intestines. After evaluating late complications, the dose constraints on the GI tracts were set under 60 GyE to prevent major complications. Thereafter, the incidence of major GI complications markedly decreased. CONCLUSION: Our findings demonstrated the characteristic histopathological effects of carbon ion radiotherapy and thus are expected to facilitate future additional applications of carbon ion radiotherapy for the treatment of gastrointestinal cancers.

Effectiveness of Roux-en-Y reconstruction after distal gastrectomy based on an assessment of biliary kinetics.

PURPOSE: To evaluate the efficiency of Roux-en-Y reconstruction (RY) after distal gastrectomy we compared postoperative physiological functions and disorders among patients who underwent RY, conventional Billroth I reconstruction (BI), or Billroth II reconstruction (BII). METHODS: The subjects were 91 patients who had undergone distal gastrectomy for gastric cancer more than 1 month earlier. To examine the severity of gastroesophageal reflux, acid reflux and alkali reflux were assessed, and to examine the severity of duodenal reflux into the remnant stomach, biliary scintigraphy was performed. The degree of inflammation in the esophagus and remnant stomach was examined by endoscopy. Questionnaires on postoperative complaints were sent out to the patients to determine how serious their reflux symptoms were. RESULTS: Both acid and alkali reflux were mild in the RY group. Biliary reflux into the remnant stomach, as assessed by biliary scintigraphy, was significantly less severe in the RY group than in the BI and BII groups. Endoscopy showed that inflammation of the lower esophagus and remnant stomach was much less severe in the RY group than in the BI and BII groups. According to the questionnaire survey, none of the patients in the RY group reported any reflux symptoms. CONCLUSIONS: In this series, RY was found to be a superior reconstruction method after distal gastrectomy since it was rarely accompanied by the reflux of duodenal juice into the remnant stomach or gastric reflux into the lower esophagus.

Prognostic significance of serum thymidine phosphorylase concentration in esophageal squamous cell carcinoma.

BACKGROUND: Thymidine phosphorylase (dThdPase), which also is referred to as platelet-derived endothelial cell growth factor, is a potent inducer of angiogenesis in malignant tumors. Increased dThdPase expression and activity have been found to be associated with poor prognosis in various solid tumor tissues. Because very little was known about the significance of serum dThdPase concentration (S-dThdPase), the objective of this study was to analyze the clinicopathologic significance of S-dThdPase in the patients with esophageal squamous cell carcinoma. METHODS: The S-dThdPase was measured by enzyme-linked immunosorbent assay in 77 healthy controls and 153 patients with primary esophageal squamous cell carcinoma. A total of 80 patients underwent surgery alone; 46 patients received chemoradiotherapy alone; 17 patients received chemoradiotherapy followed by surgery; and 10 patients did not receive any treatment. Thymidine phosphorylase expression in esophageal carcinoma tissues was examined by immunohistochemistry. The clinicopathologic value and prognostic value of S-dThdPase was determined in 80 patients treated by surgery alone. RESULTS: The S-dThdPase is significantly higher in patients with esophageal carcinoma than in healthy controls (30.8 +/- 31.8 ng/mL vs. 13.8 +/- 7.6 ng/mL; P < 0.001). Statistically significant differences in S-dThdPases were observed depending on tumor size (P < 0.01) and tumor depth (P < 0.01). A S-dThdPase of more than 29.0 ng/mL (which represented the mean plus 2 standard deviation of the concentration in healthy controls) was associated with dThdPase expression (P = 0.022), poor response (P = 0.022), and poor survival (P < 0.01). Because S-dThdPase was associated with tumor depth, S-dThdPase was not an independent prognostic factor (P = 0.095). CONCLUSIONS: A high S-dThdPase is associated with depth of tumor invasion and poor response to treatment.

Elevation of preoperative serum C-reactive protein level is related to poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: An increased serum C-reactive protein (CRP) level was found in patients with various malignant tumors and was associated with poor prognosis. The aim of this study was to analyze the clinicopathological significance and the prognostic value of preoperative CRP levels in patients with esophageal squamous cell carcinomas. PATIENTS AND METHODS: The preoperative CRP level was measured by enzyme-linked immunosorbent assay (ELISA) in 150 patients with primary esophageal squamous cell carcinomas. All patients underwent radical surgery without any preoperative therapy. The patients were divided into two groups using a cut-off value of 1.0 mg/dl. The pathological classifications of the tumor were examined according to the TNM/UICC classification. The associations between the clinicopathological factors and CRP level were determined. The prognostic value of CRP was determined using Cox's proportional hazards model. RESULTS: Thirty-five patients (23%) showed high CRP levels (more than 1.0 mg/dl). Statistically significant differences in CRP levels were observed depending on tumor depth (P = 0.022) and TNM/UICC stage (P = 0.001). A high CRP level was associated with poor survival (P = 0.005) and was confirmed by multivariate analysis. CONCLUSIONS: A high CRP level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma.

High preoperative serum midkine concentration is associated with poor survival in patients with esophageal cancer, even after radical surgery, and thus may have prognostic value. Midkine (MK), a heparin-binding growth factor, is expressed in numerous cancer tissues, and serum MK (S-MK) concentrations are increased in patients with various neoplasms. The aim of this study is to evaluate the clinical significance of S-MK in patients with esophageal squamous cell cancer (SCC). S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 93 patients with primary esophageal SCC before surgery. The serum concentrations of carcinoembryonic antigen (CEA), SCC antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated. All patients with esophageal SCC underwent radical esophagectomy. Tumor MK expression was assessed by immunohistochemistry in 14 fresh tumor specimens. To determine whether S-MK is of value as a prognostic factor, the authors conducted a survival analysis using Cox's proportional hazards model. S-MK values in patients with esophageal SCC were significantly higher than those in healthy controls (417 +/- 342 pg/ml vs. 154 +/- 76 pg/ml, P < 0.001). Using 300 pg/ml as the cut-off value (representing the mean + 2 standard deviations of the S-MK of healthy controls), 61% of patients with esophageal SCC were classified as positive. MK expression by the tumor was significantly associated with high level of S-MK. High S-MK (>/= 300 pg/ml) was associated with tumor size, immunoreactivity and poor survival. Multivariate analysis indicated that S-MK was an independent prognostic factor. S-MK may be a useful tumor marker for esophageal SCC. Increased preoperative S-MK in patients with esophageal SCC is associated with poor survival.