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This study analyzed the outcomes of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy and DCF plus concurrent radiotherapy (DCF-RT), both followed by conversion surgery, if possible, in patients with cT4b esophageal cancer.Forty-six patients with cT4b esophageal cancer, including borderline cT4b lesions, were eligible. Borderline cT4b lesions were treated with induction DCF therapy. For definitive cT4b lesions, definitive DCF-RT was administered. Patients unsuitable for induction DCF therapy or DCF-RT were treated with other therapies. After treatment, conversion surgery (CS) was performed for the residual tumor in resectable cases.Induction DCF therapy was administered to 12 patients (group A), and DCF-RT was provided to 18 patients (group B). Meanwhile, other therapies were provided to 16 patients (group C). The 1-, 3-, and 5-year overall survival (OS) rates were 66.7, 30.0, and 15.0%, respectively, in group A; 66.7, 37.5, and 37.5%, respectively, in group B; and 62.5, 0, and 0%, respectively, in group C. DCF-RT tended to prolong survival, albeit without significance (p=0.1040). The group A + B had significantly better overall survival than group C (p=0.0437). Fourteen patients underwent CS (30.4%), and patients who underwent CS had significantly better overall survival than those who did not undergo surgery (p=0.0291).Induction DCF or DCF-RT is promising for the treatment of cT4b esophageal cancer. Effective CS including combined resection of the invaded organ can contribute to improved therapeutic outcomes.

Background/aim Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to cure. C4d is a degradation product of the classical complement pathway and is suggested as an early diagnostic marker for other SCCs. The purpose of this study was to clarify the association of complement C4d with ESCC. Patients and methods Immunohistochemical staining for C4d was performed on surgical specimens obtained from 114 patients with ESCC. Results Positive C4d expression was observed in 70 (61.4%) cases and negative expression in 44 (38.6%) cases. There was a significant inverse correlation between C4d expression and depth of tumor invasion (p=0.0001), lymph node metastasis (p=0.011), lymphatic invasion (p=0.033), and TNM stage (p=0.0021). Kaplan-Meier analysis showed that negative C4d expression tended to lead to shorter overall survival (p=0.232). Conclusion C4d expression in ESCC might be useful in developing treatment strategies or suppression of ESCC.

BACKGROUND/AIM The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). PATIENTS AND METHODS The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. RESULTS Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. CONCLUSION Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUVmax DCF therapy are associated with early disease relapse and death.

The purpose of the present study was to improve the diagnostic precision of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemotherapy (NAC) in patients with advanced esophageal cancer.Thirty patients underwent FDG-PET/CT before and after NAC. The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) were measured. Patients were divided into two pathological response groups: "responders" (grades 1b-3) or "non-responders" (grades 0-1a).Overall, 11 patients were responders. Significant differences were present for the post-NAC SUVmax (p=0.070), %decrease in SUVmax (p=0.017), post-NAC MTV (p=0.014), and %decrease in MTV (p=0.003).Receiver operating characteristic curve analysis showed that the %decrease in MTV of the primary tumor was the best indicator of response to NAC. We are currently striving to improve the accuracy of this assessment method.

Patients with oesophageal squamous cell carcinoma (ESCC) have a poor prognosis. Akt has been associated with malignant potential in several cancers, including ESCC. Pleckstrin homology-like domain, family A, member 3 (PHLDA3) has been identified as a direct target gene of p53 and as a potent inhibitor of Akt activation. The present study investigated the role of PHLDA3 expression and its ability to predict prognosis in patients with ESCC who did not receive induction therapy.The intensity of PHLDA3 expression was immunohistochemically analyzed in tumor and adjacent normal tissue samples from 84 patients with ESCC, 22 who underwent endoscopic submucosal dissection and 62 who underwent thoracic oesophagectomy.High expression of PHLDA3 was observed in 60 (71.4%) patients and low expression in 24 (28.6%). Cancer-specific (p=0.029) and disease-free (p0.001) survival rates were significantly lower in the PHLDA3 low-than in the PHLDA3 high-expression group, and low PHLDA3 expression was an independent predictor of postoperative recurrence (relative risk (RR)=0.38; 95% confidence interval (CI)=0.166-0.78; p=0.0074).Low PHLDA3 expression in ESCC may be predictive of tumor recurrence suggesting that Akt activation may be a therapeutic target in ESCCs.

Currently, there is no effective therapy for advanced gastric cancer. In this study, we investigated whether protein expression of CXCL12 and/or its receptor CXCR4 is associated with clinicopathological features and/or survival of gastric cancer.Primary tumor specimens from patients (n=137) with pathologically-confirmed gastric cancer, collected between 2001 and 2009, were analyzed by immunohistochemistry using anti-CXCL12 and anti-CXCR4 antibodies.Expression of CXCL12 was directly associated with tumor differentiation (p=0.0143) but inversely associated with depth of invasion (p=0.0255), lymphatic invasion (p=0.0173), venous invasion (p=0.0022) and stage (p=0.049). Expression of CXCR4 was associated with depth of invasion (p=0.005) and stage (p=0.028). Increased CXCR4 expression, but not CXCL12 expression, was associated with 5-year cancer-specific survival (p=0.0079).CXCL12 was not associated with survival. Positive CXCR4 expression in gastric carcinoma was significantly associated with poor survival and, therefore, may be a potential biomarker for predicting poor survival.

We have previously reported that prealbumin and albumin may be sensitive indicators of the risk of recurrent disease in colorectal cancer; however, the relationship between preoperative prealbumin and cancer survival has not been fully-elucidated. The purpose of this study was to examine the relationship between preoperative nutritional conditions, including prealbumin and albumin concentrations, and the risk of recurrence in cases with breast cancer.One hundred and fifty-seven patients who underwent breast surgery were analyzed in this study. The detection limit of the prealbumin assay was 22 mg/dl; patients were divided in analytical groups of22 mg/dl and ≥22 mg/dl. The detection limit of the albumin assay was 4.0 g/dl; patients were divided in analytical groups of4.0 g/dl and ≥4.0 g/dl. The clinical features of these cases were reviewed according to prealbumin and albumin levels, and statistical analysis was performed.Among 157 cases in this study, five (3.2%) had disease recurrence. Out of the eligible cases, 38 (24.2%) had decreased serum prealbumin and 19 (12.1%) had decreased serum albumin preoperatively. No statistically significant association of the preoperative prealbumin level was found with the clinicopathological variables. The only statistically significant association found for preoperative albumin level was age; age was higher in patients with low albumin levels. In short, we were unable to establish a connection between preoperative prealbumin or albumin and various clinical features, including recurrence, lymph node metastasis and tumor size.Prealbumin and albumin may be sensitive indicators of disturbances in protein metabolism, and reflect inflammation activity and malnutrition. However, our results suggest that evaluation of serum prealbumin and albumin are not useful for predicting disease aggressiveness or recurrence in breast cancer.

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

We previously showed that the presence of vascular invasion, but not lymphatic invasion, was a strong prognostic factor for breast cancer. Lymphatic invasion may represent mainly the selective affinity of cancer cells for lymph nodes. The present study was undertaken to evaluate the presence of vascular invasion that may reflect systemic disease as a predictor of disease recurrence in colorectal cancer, separate from lymphatic invasion of the primary tumor.We retrospectively evaluated the cases of 177 consecutive patients with primary colorectal cancer who underwent colorectal resection. We examined the relationship between recurrence and the prognostic significance of clinicopathological factors, particularly lymphatic and vascular invasion.The presence of vascular invasion (v) was significant, while that of lymphatic invasion (ly) was not significant in univariate analysis. The presence of vascular invasion was an independent prognostic factor in multivariate analysis. Among the 60 patients in the ly-/v- group, one (1.7%) had disease recurrence, and among the 33 patients in the ly+/v- group, one (3.0%) had disease recurrence. On the other hand, among the 71 patients in the ly+/v+ group, 16 patients (22.5%) suffered recurrence, and among the 13 patients in the ly-/v+ group, four (30.8%) suffered recurrence. It is interesting to note that despite the presence of lymphatic invasion, the group without vascular invasion (ly+/v-) had a few patients with distant metastases, a result which is similar to that of the ly-/v- group.The presence of vascular invasion, but not lymphatic invasion, could be an indicator of high biological aggressiveness and may be a strong prognostic factor for colorectal cancer.

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method.Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival.Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival.Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Galectin-3, a beta-galactoside-binding protein, has been associated with various biological processes, such as cell adhesion, recognition, proliferation, differentiation and apoptosis. The aim of this study was to determine the relationship of galectin-3 expression to clinicopathological findings in patients with colorectal cancer. Furthermore, the correlation between the expression of galectin-3 and beta-catenin, and the Ki-67 labeling index were investigated.Immunohistochemical assessment of galectin-3, beta-catenin and Ki-67 expression was performed on samples from 108 patients with colorectal cancer. The expression of galectin-3 was classified at the tumor surface and the invasive front, and its relationship with clinicopathological factors was considered from a statistical viewpoint.There was significant liver metastasis when the expression of galectin-3 was lower at the invasive front of a tumor compared to its surface (p = 0.04). There were also significant correlations between beta-catenin expression at the tumor surface and liver metastasis and tumor stage (p = 0.03, p = 0.04 respectively).The reduction of galectin-3 expression is associated with the invasion and metastasis of colorectal cancer. A possible involvement of galectin-3 expression in tumor invasion, metastasis and proliferation in patients with colorectal cancer is suggested.