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One of the most important application of artificial intelligence (AI) in pathology is prediction, using morphological features, of patient prognosis and response to specific treatments. As one of the most common kinds of malignancies in the world and the crucial important cause of death due to malignant tumor among women, breast cancer has become the center of attention in clinical services. Axillary lymph node metastasis is an important prognostic factor in breast cancer. The accuracy of the assessment of axillary lymph node metastasis bears heavily on clinical diagnosis and treatment. At present, based on the principle of non-invasive procedures, many studies have been done to develop models that can be used to predict sentinel lymph node metastasis of breast cancer. However, different clinical and pathological parameters are used in these predictive models. How to analyze the clinical and pathological data of breast cancer patients in a more comprehensive way and how to establish a prediction model with better precision have become the future direction of development. In this paper, we describe the research progress of AI in pathology and the current status of its use in breast cancer research. We have conducted in-depth reflection and looked into the future of ways to predict effectively breast cancer lymph node metastasis and to establish more accurate and effective deep-learning algorithm based on AI assistance so as to continuously improve the diagnosis and treatment of breast cancer., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1-2N1M0 breast cancer., Methods: A total of 4262 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method., Results: At a median follow-up of 71 months (range of 6-230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis., Conclusion: Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1-2N1M0 breast cancer.

Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. The present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. Next-generation sequencing showed that TCN1 was one of several upregulated mRNAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan-Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity.

Background: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy., Methods: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962., Findings: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001)., Interpretation: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients., Funding: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

As a multi-stage disorder, Alzheimer's disease (AD) is quickly becoming one of the most prevalent neurodegenerative diseases worldwide. Thus, a non-invasive, serum-based diagnostic platform is eagerly awaited. The goal of this study was to identify a serum-based biomarker panel using a predictive protein-based algorithm that is able to confidently distinguish AD patients from control subjects. One hundred and fifty-six patients with AD and the same number of gender- and age-matched control participants with standardized clinical assessments and neuroimaging measures were evaluated. Serum proteins of interest were quantified using a magnetic bead-based immunofluorescent assay, and a total of 33 analytes were examined. All of the subjects were then randomized into a training set containing 70% of the total samples and a validation set containing 30%, with each containing an equal number of AD and normal samples. Logistic regression and random forest analyses were then applied to develop a desirable algorithm for AD detection. The random forest method was found to generate a more robust predictive model than the logistic regression analysis. Furthermore, an eight-protein-based algorithm was found to be the most robust with a sensitivity of 97.7%, specificity of 88.6%, and AUC of 99%. Our study developed a novel eight-protein biomarker panel that can be used to distinguish AD and control multi-source candidates regardless of age. It is hoped that these results provide further insight into the applicability of serum-based screening methods and contribute to the development of lower-cost, less invasive methods for diagnosing AD and monitoring progression.

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) are two main radiotherapy techniques. The aim of this study is to explore which is the preferred technique in prostate treatment through the related publica-tions and meta-analysis. Two authors independently identified all relevant articles available regarding eligibility criteria on PubMed, Embase, and Cochrane Library databases until December 2015. Publication bias was evaluated with funnel plot, and statistical analyses were performed with Stata software. P < 0.05 was thought statistically significant. Ten studies comprised a total of 110 patients; in total 110 IMRT plans and 110 VMAT plans that were included in this study. V40, V60, and V70 of rectum were significantly decreased in VMAT than in IMRT. However, V50 of rectum and V40, V50, V60, V70 of bladder had no statistical differences between IMRI and VMAT plans. Compared with IMRT, the treatment time and MUs of VMAT were significantly lower. VMAT protects rectum better than IMRT and improves the delivery efficiency. VMAT may be the preferred modality for treating prostate cancer., (© 2016 The Authors.)

Clinical differences between anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK(-) ALCL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remain unclear. The aim of this study was to compare the clinical and prognostic features of these two lymphoma types. We retrospectively analyzed 167 patients with ALK(-) ALCL (n = 48) and PTCL-NOS (n = 119). Compared with ALK(-) ALCL patients, PTCL-NOS patients exhibited distinct differences in clinical features with a propensity for more advanced stages, frequent extranodal involvement, and a poor performance status, leading to a higher risk group according to the International Prognostic Index or Prognostic Index for PTCL-NOS. Patients with ALK(-) ALCL were associated with a higher complete response rate (47.9 vs. 31.0 %; P = 0.041) after initial chemotherapy than patients with PTCL-NOS. The prognosis was significantly different between two subtypes, with a 5-year overall survival (OS) rate of 57.9 % for ALK(-) ALCL and 23.9 % for PTCL-NOS (P = 0.002). The subgroup analysis showed significant differences in OS and progression-free survival between the two subtypes in early-stage diseases, but not in advanced-stage diseases. We conclude that patients with ALK(-) ALCL showed favorable clinical features, higher chemosensitivity, and a superior outcome than those with PTCL-NOS.

Three-dimensional conformal radiotherapy in combination with transarterial chemoembolization (TACE) has been beneficial in patients with unresectable hepatocellular carcinoma (HCC). There have been few clinical reports on the use of intensity-modulated radiotherapy (IMRT) in combination with TACE for these patients. The purpose of this study was to assess the efficacy and toxicity of IMRT following TACE in unresectable HCC.The medical records of consecutive patients with unresectable HCC, who underwent IMRT following TACE from January 2009 to June 2014, were retrospectively reviewed in order to assess the overall survival (OS), progression-free survival (PFS), tumor response, and treatment-associated toxicity.A total of 64 lesions in 54 patients were included in the analysis. IMRT was delivered at a median dose of 50 Gy (range 44-70 Gy) at 1.8 to 2.0 Gy per fraction. The overall response rate was achieved in 64.8% of patients with complete response in 20.4% of patients at 3 months after completion of IMRT. The median OS was 20.2 months (95% CI = 8.6-31.9), and the actuarial 1-, 2-, and 3-year OS rates were 84.6%, 49.7%, and 36.7%, respectively. The median PFS was 10.5 months (95% CI = 7.3-13.7) and the 1-, 2-, and 3-year PFS rates were 44.2%, 23.4%, and 14.6%, respectively. The responders had a significantly higher OS rate than the nonresponders (3-year OS 48.0% vs 14.4%, P = 0.001). During and the first month following IMRT, 10 (18.5%) patients developed grade 3 hematological toxicity, and 3 (5.6%) developed grade 3 hepatic toxicity. No patient experienced grade 4 or 5 toxicity. Radiation-induced liver disease was not observed.Our findings suggest that IMRT following TACE could be a favorable treatment option for both its safety profile and clinical benefit in patients with unresectable HCC.

Background: Non-invasive blood-based biomarkers are eagerly awaited for the diagnosis of Alzheimer's disease (AD). The present study aimed to evaluate the individual and combined diagnostic value of soluble CD40 ligand (sCD40L) and vascular endothelial growth factor (VEGF) for AD., Methods: Fifty patients with AD and forty gender and age-matched control participants with standardized clinical assessments and neuroimaging measures were enrolled. VEGF and sCD40L were qualified in 90 subjects using immunomagnetic beads assay., Results: To evaluate the individual and combined diagnostic value of sCD40L and VEGF for AD, receiver operating characteristic curves were generated and logistic regression analysis was conducted. The AUCs (area under ROCs) of sCD40L and VEGF and their corresponding 95% confidence interval (CI) were 0.824 (95% CI: 0.737-0.910) and 0.731 (95% CI: 0.622-0.839), respectively. Combined ROC analysis based on these 2 biomarkers revealed an elevated AUC of 0.858 (95% CI: 0.775-0.941), which indicates an additive effect in the diagnostic value of these two biomarkers., Conclusions: We identified the feasibility of a blood-based biomarker approach in AD diagnostics though the results warrant validation in large-scale studies. A combination of sCD40L and VEGF could be a useful diagnostic biomarker for future clinical trials with AD and may act as a suitable add-on biomarker to the panel of markers already existing for AD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background & Aims: To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels., Methods: This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups., Results: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease., Conclusions: Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A decrease in the number of dendritic cells (DCs) is a major cause of post-sepsis immunosuppression and opportunistic infection and is closely associated with poor prognosis. Increasing the number of DCs to replenish their numbers post sepsis can improve the condition. This therapeutic approach could improve recovery after sepsis. Eighty C57BL/6 mice were subjected to sham or caecal ligation and puncture (CLP) surgery. Mice were divided into four groups: (i) Sham + vehicle, (ii) Sham + DC, (iii) CLP + vehicle, and (iv) CLP + DC. Bone-marrow-derived DCs (BMDCs) were administered at 6, 12 and 24 hr after surgery. After 3 days, we assessed serum indices of organ function (alanine aminotransferase, aspartate aminotransferase, creatinine, amylase and lipase), organ tissue histopathology (haematoxylin and eosin staining), cytokine [interferon-γ (IFN-γ), tumour necrosis factor-α, interleukin-12p70 (IL-12p70), IL-6 and IL-10] levels in the serum, programmed death-1 (PD-1) expression on T cells, regulatory T-cell differentiation in the spleen, and the survival rate (monitored for 7 days). BMDC transfer resulted in the following changes: a significant reduction in damage to the liver, kidney and pancreas in the CLP-septic mice as well as in the pathological changes seen in the liver, lung, small intestine and pancreas; significantly elevated levels of the T helper type 1 (Th1) cytokines IFN-γ and IL-12p70 in the serum; decreased levels of the Th2 cytokines IL-6 and IL-10 in the serum; reduced expression of PD-1 molecules on CD4(+) T cells; reduced the proliferation and differentiation of splenic suppressor T cells and CD4(+)  CD25(+)  Foxp3(+) regulatory T cells, and a significant increase in the survival rate of the septic animals. These results show that administration of BMDCs may have modulated the differentiation and immune function of T cells and contributed to alleviate immunosuppression, hence reducing organ damage and mortality post sepsis. Hence, the immunoregulatory effect of BMDC treatment has potential for the treatment of sepsis., (© 2014 John Wiley & Sons Ltd.)

Background: The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection., Methods: Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS)., Results: At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy., Conclusions: The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels.

Aim: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer., Methods: We enrolled patients with any T stage and node-positive gastroesophageal or gastric adenocarcinoma after complete resection with negative margins (R0) or microscopic (R1) or macroscopic (R2) resection. Intensity modulated radiotherapy (IMRT) using a five-to-seven-field, coplanar, sliding window technique was delivered to the tumor bed (T4b), anastomosis site, duodenal stump and regional lymph nodes (LNs) to a total dose of 45 Gy (1.8 Gy/fraction, 5 d/wk). Patients with R1 or R2 resection received 10.8 Gy as a boost. Capecitabine was administered twice daily on every radiotherapy treatment day in a dose-escalation schedule (mg/m²) of 625 (level I, n = 6), 700 (level II, n = 6), 800 (level III, n = 6), 900 (level IV, n = 0) and 1000 (level V, n = 0). DLT was defined as grade 4 leukopenia or neutropenia, grade 3-4 thrombocytopenia or anemia and grade 3-4 non-hematological toxicity., Results: Between October 2007 and August 2009, 18 patients (12 men, 6 women; median age, 54 years) were enrolled in the study. The median number of positive LNs was 6, and total number of resected LNs was 19. Twelve patients underwent R0 resection (66.7%). Fifteen patients received adjuvant chemotherapy under the leucovorin, fluorouracil and oxaliplatin (FOLFOX4) regimen. Six patients each were enrolled at dose levels I, II and III. Grade 1-3 leukopenia (16 patients, 88.9%), anorexia (15, 83.3%) and nausea (15, 83.3%) were the most common toxicities. Grade 3 anorexia/nausea and grade 4 vomiting occurred in one level-I patient. Grade 3 anorexia and nausea occurred in one level-II patient. One level-III patient developed grade 4 neutropenia, while another developed grade 3 radiation esophagitis. No abnormal liver or renal function examinations were observed. Three patients did not finish chemoradiotherapy because of DLTs and two without DLTs received sequential boosts (total dose, 55.8 Gy)., Conclusion: The MTD of capecitabine was 800 mg/m² twice daily concurrent with IMRT for gastric cancer after surgery. The DLTs were anorexia/nausea, vomiting, neutropenia and radiation esophagitis.

Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan-Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525 ± 1.233 vs. 1.512 ± 0.784, P < 0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P = 0.026), histological differentiation (P = 0.039), tumor stage (P = 0.006), and the presence of metastasis (P < 0.001). Moreover, Kaplan-Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P < 0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.

Colorectal cancer (CRC) is a common malignancy with a high incidence and mortality rate. Recent studies have pointed to deregulation of autophagy as a novel pathogenesis of human malignancy. SM22 is considered as a tumor suppressor. The aim of the present study was to evaluate the correlation of the SM22 expression level with the autophagy activity and the clinical characteristics in human CRC tissues. The expressions of SM22 and p62, a biomarker of autophagy activity, in paired tumor and adjacent non-tumor tissues from 43 patients with colorectal cancer were detected by western blot and immunohistochemical staining, respectively. The results showed that the SM22 level decreased significantly in 81.4% CRC tissues, while the expression of p62 increased in 79.1% cases. There was a negative correlation between p62 and SM22 expressions in colorectal cancer tissues (p=0.004). Similarly, the negative correlation between SM22 and p62 was verified in human CRC cell lines. The data suggest that the autophagy activity decreased in human CRC, which was associated with reduction in SM22 expression. However, the expression of SM22 was not associated with the gender, tumor site and Duke's stage of the patients. In conclusion, our findings suggest that the disruption of SM22 may be involved in tumorigenesis in CRC. The autophagic activity may be suppressed in human CRC, and SM22 may act as a positive regulator in the processes of autophagy., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

The clinical value of plasma Epstein-Barr virus (EBV) DNA has not been evaluated in patients with early-stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) receiving primary radiotherapy. Fifty-eight patients with stage I disease and 11 with stage II disease were recruited. High pretreatment EBV-DNA concentrations were associated with B-symptoms, elevated lactate dehydrogenase levels, and a high International Prognostic Index score. EBV-DNA levels significantly decreased after treatment. The 3-year overall survival (OS) rate was 82.6% for all patients. Stage I or II patients with a pretreatment EBV-DNA level of ≤ 500 copies/mL had 3-year OS and progression-free survival (PFS) rates of 97.1% and 79.0%, respectively, compared with 66.3% (P = .002) and 52.2% (P = .045) in patients with EBV-DNA levels of > 500 copies/mL. The 3-year OS and PFS rates for patients with undetectable EBV-DNA after treatment was significantly higher than patients with detectable EBV-DNA (OS, 92.0% vs 69.8%, P = .031; PFS, 77.5% vs 50.7%, P = .028). Similar results were observed in stage I patients. EBV-DNA levels correlate with tumor load and a poorer prognosis in early-stage NKTCL. The circulating EBV-DNA level could serve both as a valuable biomarker of tumor load for the accurate classification of early-stage NKTCL and as a prognostic factor.

Objective: To explore the expression of PI3K in esophageal squamous cell carcinoma (ESCC) and its clinical significance., Methods: The expression of PI3K proteins was detected by immunohistochemical SP staining in 91 ESCC tissues and normal mucosa of 10 cases. RT-PCR was used to detect the expression of PI3K mRNA in 30 ESCC tissues and adjacent normal mucosa. The relation between PI3K expression and the clinicopathological features and prognosis was analyzed., Results: The positive rate of expression of PI3K protein in ESCC was 86.8%, significantly higher than that in normal esophageal mucosa (10.0%, P<0.001). There was a positive correlation between P13K expression and the degrees of differentiation, invasion depth, and clinical stage. No positive correlation was found between the expression of PI3K protein and age, gender and lymph node metastasis (P>0.05). The poorer is the differentiation of ESCC, the stronger is expression of PI3K protein (r = 0.351, P<0.05); the deeper is the invasion depth of ESCC, the stronger is expression of PI3K protein (r = 0.210, P<0.05); and the higher is the clinical stage of ESCC, the stronger expression of PI3 K protein (r = 0.240, P<0.05). RT-PCR results demonstrated that the level of PI3K mRNA expression in ESCC was 0.675 +/- 0.029, significantly higher than that in the adjacent normal mucosa (0.349 +/- 0.073, P<0.05). The high expression of PI3K mRNA was correlated with poor differentiation, deep invasion and clinical stage of ESCC (P<0.05). The result was consistent with SP staining immunohistochemistry. By Kaplan-Meier analyses, following factors were observed to be significantly associated with prognosis: PI3K expression, the degrees of differentiation, invasion depth, lymph node metastasis, clinical stage, tumor embolus and stump invaded (all P<0.05). The multivariate analysis showed that clinical stage (P<0.05), invasion depth (P<0.05) and stump invaded (P<0.05) were significantly correlated with the prognosis. The multivariate analysis of Cox model showed that PI3K was not an independent prognostic indicator of prognosis (chi2 = 1.235, P = 0.266)., Conclusions: The expression levels of PI3K protein and mRNA in ESCC tissues are significantly increased and PI3K plays a role in the carcinogenesis and development of ESCC. The enhanced PI3K expression may serve as a reference index indicating a poor prognosis in ESCC.

Objective: To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy., Methods: The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS)., Results: 141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS., Conclusion: ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

Extranodal nasal-type natural killer (NK)/T-cell lymphoma is rarely observed in children and adolescents. We aim to investigate the clinical features, prognosis, and treatment outcomes in these patients. Thirty-seven patients were reviewed. There were 19, 14, 2, and 2 patients with stage I, stage II, stage III, and stage IV diseases, respectively. Among the patients with stage I and II disease, 19 patients received initial radiotherapy with or without chemotherapy, and 14 patients received chemotherapy followed by radiotherapy. The 4 patients with stage III and IV disease received primary chemotherapy and radiation of the primary tumor. Children and adolescents with extranodal nasal-type NK/T-cell lymphoma usually presented with early-stage disease, high frequency of B symptoms, good performance, low-risk age-adjusted international prognostic index, and chemoresistance. The complete response rate after initial radiotherapy was 73.7%, which was significantly higher than the response rate after initial chemotherapy (16.7%; P = .002). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all the patients were 77.0% and 68.5%, respectively. The corresponding OS and PFS rates for patients with stage I and II disease were 77.6% and 72.3%, respectively. Children and adolescents with early-stage extranodal nasal-type NK/T-cell lymphoma treated with primary radiotherapy had a favorable prognosis.

Objective: To analyze the role of postmastectomy radiotherapy (PMRT) in moderate- and high-risk elderly breast cancer patients., Methods: The clinicopathological data of 874 breast cancer patients treated with mastectomy and axillary dissection were retrospectively analyzed. The T1-2N1 patients were defined as moderate- risk (IR) group, and T3-4 and/or N2-3 cases as high-risk (HR) group. The locoregional recurrence (LRR) and overall survival (OS) rates were calculated and compared according to different age groups and radiotherapy status. Kaplan-Meier method and Log-rank test was used for calculation and comparison of the survival curves of different patient groups., Results: The median follow up time was 47 months. 108 (12.4%) patients were > or = 65 years. For patients who were < 65 and > or = 65 years, 18.1% and 15.3% received PMRT in the IR group, and 82.7% and 52.2% received PMRT in the HR group, respectively. For patients > or = 65 years, the 5-year LRR rates were 0% and 14.2% (P = 0.242) and 5-year OS rates were 100% and 75.2% (P = 0.159) for the PMRT-IR and non-PMRT-IR groups, respectively. The 5-year LRR rates were 0% and 14.1% (P = 0.061), 5-year OS rates were 84.6% and 77.4% (P = 0.597) for the PMRT-HR and non-PMRT-HR groups, respectively. For patients < 65 years, the 5-year LRR rates were 0% and 9.9% (P = 0.035) and 5-year OS rates were 87.0% and 82.1% (P = 0.739) for the PMRT-IR and non-PMRT-groups, respectively. The 5-year LRR rates were 7.2% and 26.1% (P = 0.000), 5-year OS rates were 79.2% and 57.7% (P = 0.000) for the PMRT-HR and non-PMRT-HR groups, respectively., Conclusion: With the increasing of age, there is a trend of decreasing use of postmastectomy radiotherapy in high-risk breast cancer patients. Postmastectomy radiotherapy can improve the locoregional control for high-risk patients and maybe considered even for those who are > or = 65 years.

Background and Objective: Both RhoA and Ezrin are confirmed to play an important role in the development and metastasis of tumors. However, the mechanism remains unclear. This study rudimentally investigates the regulatory effect of RhoA on the expression of Ezrin., Methods: After MDA-MB-231 cells were treated with epidermal growth factor (EGF) or following pretreatment of fasudil (the special inhibitor of RhoA), the expression of RhoA, p-RhoA and Ezrin in MDA-MB-231 cells was detected by western blot., Results: Stimulation of EGF triggered RhoA phosphorylation in MDA-MB-231 cells which reached the maximum at 30 min; RhoA expression did not change; Ezrin expression was enhanced and reached the maximum at 24 h. However, pretreatment of fasudil before EGF stimulation decreased RhoA phosphorylation and Ezrin expression in MDA-MB-231 cells by 72.73% and 51.28%, respectively., Conclusion: RhoA may regulate the invasion and metastasis of breast cancer cells as an upstream signaling of Ezrin.

Objective: To investigate the changes of gene expression profile in nasal NK/T cell lymphoma., Methods: Total RNA was extracted from the fresh nasal NK/T cell lymphoma tissue and normal lymph node. Fluorescent labeled cDNA was obtained through synthesizing process by reverse transcription. After hybridization in the two identical microarrays consisting of 4096 genes, overexpressed or underexpressed tumor related genes were analyzed., Results: In both experimental group and control group, there were six samples. A total of 365 (8.9%) genes was found to be differentially expressed by a factor of twofold or greater in both of two identical cDNA microarrays, which included oncogenes, tumor supressor genes, cell cycle regulators, apoptotic and antiapoptotic factors, DNA transcription factors, DNA repair and recombination factors, signal transduction genes, protein translation genes, as well as a large number of metabolic genes. Thirty-seven of these genes were found to be differentially expressed by a factor of fourfold or greater. The biochemical functions of these differentially expressed genes were diverse., Conclusion: This study demonstrates that many different kinds of genes are possibly involved in the initiation and progression of nasal NK/T lymphoma. cDNA microarray technique is useful in screening cancer gene expression for nasal NK/T lymphoma.

Objective: This phase I study is to determine the maximal tolerated dose and the dose-limiting toxicity of capecitabine combined with standard radiotherapy (RT) as postoperative adjuvant treatment for rectal cancer patients., Methods: Stage II/III rectal cancer patients 18 - 75 years of age had undergone curative surgery with Karnofsky score > or = 70% were eligible to be included in this study. Total dose of RT DT 50 Gy was delivered to the pelvic area in fraction of 2.0 Gy per day for 5 weeks. Capecitabine was orally administered concurrently with radiotherapy for a total of 2 cycles in escalating doses: twice daily at 12 hour interval for consecutive 14 days as one cycle, separated by a seven day rest, then followed by another cycle. From March 2004 to May 2005, 24 patients were included and treated at the following dose levels: daily 1000 mg/m(2) (3 patients), 1200 mg/m(2) (3 patients), 1400 mg/m(2) (3 patients), 1500 mg/m(2) (3 patients), 1600 mg/m(2) (6 patients), and 1700 mg/m(2) (6 patients). Dose-limiting toxicities (DLT) including grade 3 or grade 4 hematologic and nonhematologic toxicity were observed., Results: Dose-limiting toxicity was observed in one patient treated at dose of 1600 mg/m(2) with grade 3 diarrhea, and in 2 patients at dose of 1700 mg/m(2) with one grade 3 and one grade 4 diarrhea., Conclusion: Diarrhea is the most common dose-limiting toxicity. In our study, the maximal tolerated dose (MTD) of capecitabine given concurrently with radiotherapy was daily 1600 mg/m(2), from D1 to D14 separated by 7-day rest for 2 cycles. Capecitabine given concurrently with standard radiotherapy is safe and tolerable for operated stage II/III rectal cancer patients.

Objective: To evaluate whether involved-field (IF) radiotherapy is equally effective and less toxic in comparison with extended-field (EF) radiotherapy for patients with early-stage Hodgkin's disease (HD) who received combined modality therapy., Methods: The data of 88 early-stage HD patients treated with combined modality therapy were retrospectively reviewed. According to Ann Arbor classification, 12 patients (13.7%) had stage IA disease, 56 stage IIA (63.6%), and 20 IIB (22.7%). Forty-two (47.7%) patients underwent involved field radiotherapy (IF group), whereas the other 46 (52.3%) received extended field radiotherapy (EF group)., Results: Of 6 patients who developed recurrence, 3 (7.1%) were in IF group and the other 3 (6.5%) in EF group. Only one patient's recurrence developed inside the radiation field in EF group. Three patients (7.2%) in IF group and 9 (19.5%) in EF group had WHO grade 1 and 2 leukopenia (P = 0.089). Overall survival rate at 1-, 2- and 3-year was 100.0%, 97.1%, and 97.1% in IF group versus 100.0%, 100%, and 95.8% in EF group (P = 0.86), respectively. Freedom from progression survival rate at 1-, 2- and 3-year was 97.6%, 94.8%, and 91.7% in IF group versus 97.8%, 93.2%, and 93.2% in EF group (P = 0.65), respectively., Conclusion: Compared with extended-field radiotherapy, involved-field radiotherapy is equally effective and less toxic for patient with early-stage Hodgkin's disease treated with combined modality therapy.

Objective: The optimal treatment for primary non-Hodgkin's lymphoma (NHL) of the nasal cavity remains controversial. This study was to analyze the initial response rate of radiotherapy and chemotherapy, and the influence of different treatment modalities on prognosis., Methods: From January 1996 to December 2002, the clinical data of 129 patients with previously untreated nasal NHL were retrospectively reviewed with all lesions confirmed by pathology. 116 patients were morphologically diagnosed as having nasal NK/T cell lymphoma. The immunophenotype was available in 57 cases and 52 (91.2%) of them were confirmed as NK/T-cell lymphoma. According to the Ann Arbor Staging System, 102 patients had stage I(E), 22 stage II(E), and 5 stage IV(E) disease. Among the 124 patients with stage I(E) and II(E) diseases, 22 patients received radiotherapy alone, 7 chemotherapy alone, and 95 combined modality therapy (CMT). Of these 95 patients treated with CMT, 45 patients were treated with radiotherapy followed by chemotherapy, and 50 with chemotherapy followed by radiotherapy. The primary treatment for stage IV(E) patients was chemotherapy with or without radiotherapy to the primary tumor., Results: The overall 5-year survival (OS) and disease free survival (DFS) for all patients was 68.0% and 55.8%, respectively. It was 71.7% and 60.9% for stage I(E), and 70.6% and 47.0% for stage II(E), respectively (P > 0.05). The OS and DFS at the 5th year were 83.1% and 68.0% for patients who achieved complete response (CR), and 18.0% and 15.5% for those who did not, respectively (P = 0.000). Of the 124 patients with stage I(E) and II(E) disease, 67 patients were treated with radiotherapy alone (22 patients) or radiotherapy followed by chemotherapy (45), whereas 57 were treated with chemotherapy followed by radiotherapy (50) or chemotherapy alone (7). The CR rate after radiotherapy was 74.7%, however, it was only 19.3% after chemotherapy (P = 0.000). Of the 46 patients with PR, SD or PD after chemotherapy, 42 still had locoreginally localized lesion and 31 of these patients achieved CR by following radiotherapy which revealed satisfactory results. For stage I(E) and II(E) disease, the 5-year OS and DFS were 76.0% and 65.0% for radiotherapy with or without chemotherapy, and 74.4% and 56.2% for chemotherapy followed by radiotherapy. The difference was statistically not significant. However, 7 stage I(E) and II(E) patients were treated with chemotherapy alone, and 4 of them died of disease progression, with 1-year survival of 26.7%., Conclusion: The majority of Chinese patients with primary nasal NHL are NK/T cell in origin. The complete response rate by radiotherapy is much higher than that by chemotherapy. The addition of chemotherapy to radiotherapy did not improve the survival of patients with early stage nasal lymphoma. Radiotherapy is suggested as the primary treatment for stage I(E) and II(E) nasal NK/T cell lymphoma.