Soluble E-cadherin is a valid prognostic marker in gastric carcinoma

BACKGROUND: Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS: To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS: Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarcinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS: The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008-1.668) and palliative/conservative treatment (p=0.023, CI 1.038-2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION: Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.     

Towards a molecular approach to gastric cancer management

Abstract
Gastric cancer is a leading cause of cancer death worldwide. Most patients with gastric cancer present with locally advanced and incurable disease, and overall survival is poor. Considerable research efforts towards the epidemiology and pathogenesis of gastric cancer have not been translated into treatment success. We discuss current concepts of the pathogenesis of gastric cancer and how recent research advances, in particular global gene expression strategies, may improve this understanding, and suggest a framework wherein these approaches may be used. (Intern Med J 2001; 31: 296–303)     

Modern approaches to the treatment of breast cancer

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.     

The evolution of the role of surgery in the management of breast cancer lung metastasis

Breast cancer is the second leading cause of cancer death among women in the United States. Patients with metastatic disease have a median survival of 12 to 24 months and most present with disseminated disease; however, some present with isolated pulmonary metastases which may benefit from surgical resection. Although the initial experience with resection of pulmonary metastases in the late 19th and early 20th centuries produced some encouraging results, patient selection criteria for resection were strict until the mid-1960's when a significant improvement in survival resulted from aggressive management of pulmonary metastasis in osteosarcoma patients. The application of this approach to breast cancer patients similarly produced encouraging results, with five year survival rates in select patients ranging from 36-54%, but this was not without controversy. In this review, we discuss the evaluation of the breast cancer patient with a pulmonary nodule, the historical evolution of the role of surgery in the management of pulmonary metastasis, as well as the latest evidence to guide patient selection and management.     

Predictors of early distant metastasis in women with breast cancer

Background

Breast cancer is a clinically heterogeneous disease. Approximately 10–15 % of breast cancer patients develop distant metastases within 2 years of diagnosis with a poor 5-year survival rate of 21 %. Little data have been gathered about how some breast cancer metastasizes earlier than expected. The study aimed to identify predictors of distant metastases among breast cancer patients in relation to their clinical and tumour characteristics. The results of the study may have important implications in our understanding of the disease process allowing more aggressive treatment and monitoring of certain subgroups of patients.

Methodology

Retrospective review of 215 patients (54 % early stage and 46 % locally advanced stage) who fulfilled the specified criteria was performed. Twelve variables were considered. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of developing distant metastasis within 24 months after surgery and adjuvant therapy.

Results

Of the 215 patients, 27.9 and 17.7 % developed bone and visceral metastasis, respectively. Bone metastasis was significantly dependent on stage, tumour size, lymph node involvement, lymphovascular invasion, estrogen receptor, progesterone receptor and Her/2-neu pattern (p < 0.05). Visceral metastasis was significantly dependent on age, menopausal status, stage, tumour size, lymph node involvement, estrogen receptor, progesterone receptor and Her-2/neu pattern (p < 0.05). Among patients with bone and visceral metastases, 67 and 43 % have triple negative pattern, respectively. Logistic regression provided an accurate model for predicting bone but not visceral metastasis.

Conclusion

A significant fraction of breast cancer patients experienced early metastasis. Our data suggest that tumour stage, size and lymph node involvement are major predictors of metastasis. Her-2/neu over-expression alone is not a strong predictor of early metastasis but triple negative breast cancers belong to an aggressive subgroup with early metastatic capacity. Young, premenopausal patients may benefit from aggressive surveillance and treatment since they tend to present with early visceral spread.     

Hodgkin's disease and age

506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic nodal tumour burden, intraabdominal nodal tumour burden, and number of involved extranodal sites), pretreatment ESR, lymphocytopenia, and treatment modality were examined in multivariate analyses. The only factors of independent prognostic significance for disease-free survival proved to be treatment modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate treatment for relapse. The present study indicates that Hodgkin's disease in older patients is not prognostically very different from Hodgkin's disease in younger patients.     

Comparison of plasma D-dimer and thrombus precursor protein in patients with operable breast cancer as a potential predictor of lymph node metastasis.

Fibrin formation and removal is continuous during the development of malignancy. Plasma D-dimer is indicative of ongoing fibrinolysis, and circulating soluble fibrin polymer [thrombus precursor protein (TpP)] represents thrombogenic activity. We evaluated the relationship between plasma D-dimer and TpP levels with tumor extent and examined the use of these markers as possible predictors of lymph node metastasis in breast cancer. Preoperative plasma levels of D-dimer and TpP were measured in these 120 patients (93 breast cancer, 27 benign breast disease) and 29 healthy controls. Plasma levels of D-dimer in patients with breast cancer were significantly higher than in healthy controls and in those with benign breast disease. Plasma D-dimer levels in patients with breast cancer were found to be significantly increased according to tumor stage. We also observed that plasma levels of D-dimer were higher in patients with lymph node metastasis than in patients without metastasis. In contrast, TpP levels were not significantly different by the tumor stages and lymph node metastasis. In conclusion, increased D-dimer levels in breast cancer may suggest that an ongoing fibrinolysis within breast cancer tissue occurs during tumor progression. Positive D-dimer levels might be useful for identifying metastatic lymph node in patients with operable breast cancer. However, plasma TpP was not found to be a sensitive marker for detecting tumor-associated subclinical coagulopathy.     

Successful outcome after combined chemotherapeutic and surgical management in a case of esophageal cancer with breast and brain relapse

INTRODUCTION Esophageal cancer (EC) is a highly lethal disease, with an estimated annual incidence of 14 550 new cases and 13 770 related deaths in 2006 in the USA[1]. Approximately 50% of patients present with metastatic disease and most patients with lo…     

No association between serum levels of insulin-like growth factor-I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery

BACKGROUND: Angiogenesis is essential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has been suggested as the major angio-genic factor in breast carcinoma. Both insulin-like growth factor-I (IGF-I) and prolactin are involved in the progression of breast cancer at least partly by stimulating angiogenesis. AIM: The aim of the present study was to investigate the association between serum IGF-I, VEGF and prolactin levels and clinicopathological characteristics of breast carcinoma. METHODS: Serum IGF-I, VEGF and prolactin levels were measured in breast cancer patients and controls and these levels were compared with well-known clinicopathological characteristics of breast carcinoma, including tumour size, axillary lymph node and oestrogen/progesterone receptor status, tumour grade and disease stage. RESULTS: Serum prolactin, VEGF and IGF-I levels were found to be similar in breast cancer patients and control subjects (P > 0.05). When the patients were divided into groups according to their tumour size, axillary lymph node status, tumour grade, oestrogen/progesterone receptor status and disease stage, no significant differences in serum prolactin, VEGF and IGF-I levels were found among the groups (P > 0.05). CONCLUSIONS: The present study failed to demonstrate an association between serum levels of VEGF, IGF-I and prolactin and well-known clinicopathological characteristics of breast carcinoma.     

Effect of aspirin use on survival benefits of breast cancer patients: A meta-analysis

Objective:The purpose of this study is to investigate whether aspirin improves the prognosis of breast cancer patients by meta analysis.Methods:Searched PubMed, EMBASE, and other databases for literature on the relationship between aspirin use and breast cancer prognosis, with the deadline of October 2019. The related results of all-cause death, breast cancer-specific death, and breast cancer recurrence/metastasis were extracted to combine the effect amount. The sensitivity analysis and published bias analysis were carried out for the included data. Stata12.0 software was used to complete all statistical analysis.Results:A total of 13 papers were included in the study, including 142,644 breast cancer patients. The results of meta-analysis showed that patients who took aspirin were associated with lower breast cancer-specific death (HR = 0.69, 95% CI = 0.61–0.76), all-cause death (HR = 0.78, 95% CI = 0.71–0.84), and risk of recurrence/metastasis (HR = 0.91, 95% CI: 0.82–1.00).Conclusions:Aspirin use may improve all-cause mortality, specific mortality, and risk of recurrence/metastasis in patients with breast cancer.     

The macrophage-stimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans

A better understanding of tumor metastasis requires development of animal models that authentically reproduce the metastatic process. By modifying an existing mouse model of breast cancer, we discovered that macrophage-stimulating protein promoted breast tumor growth and metastasis to several organs. A special feature of our findings was the occurrence of osteolytic bone metastases, which are prominent in human breast cancer. To explore the clinical relevance of our model, we examined expression levels of three genes involved in activation of the MSP signaling pathway (MSP, MT-SP1, and MST1R) in human breast tumors. We found that overexpression of MSP, MT-SP1, and MST1R was a strong independent indicator of both metastasis and death in human breast cancer patients and significantly increased the accuracy of an existing gene expression signature for poor prognosis. These data suggest that signaling initiated by MSP is an important contributor to metastasis of breast cancer and introduce an independent biomarker for assessing the prognosis of humans with breast cancer.     

原发性心脏肿瘤八例报告

本文报道了8例非粘液瘤性的心脏原发性肿瘤(5例良性肿瘤,3例恶性肿瘤)的治疗经验、临床表现与手术情况,评价了某些临床特殊检查的价值与意义,并总结讨论了本组8例患者的诊断、治疗及预后的经验与体会。     

肺癌循环肿瘤细胞研究进展

肺癌是引起肿瘤相关死亡的首要原因.循环肿瘤细胞(CTCs)在肺癌的远处转移中起到关键作用.最近研究显示,CTCs水平可以预测肺癌患者的预后和治疗效果.CTCs检测作为一种“液体活检”具有更小的创伤性.CTCs可以及时反映患者的疾病状态,并为肺癌患者提供更好的个体化治疗策略.     

Synthetic analogues of migrastatin that inhibit mammary tumor metastasis in mice

Tumor metastasis is the most common cause of death in cancer patients. Here, we show that two, fully synthetic migrastatin analogues, core macroketone and core macrolactam, are potent inhibitors of metastasis in a murine breast tumor model. Administration of these readily accessible compounds nearly completely inhibits lung metastasis of highly metastatic mammary carcinoma cells. Treatment of tumor cells with core macroketone and core macrolactam blocks Rac activation, lamellipodia formation, and cell migration, suggesting that these chemical compounds interfere with the invasion step of the metastatic process. These compounds also inhibit the migration of human metastatic breast cancer cells, prostate cancer cells, and colon cancer cells but not normal mammary-gland epithelial cells, fibroblasts, and leukocytes. These data demonstrate that the macroketone and macrolactam core structures are specific small-molecule inhibitors of tumor metastasis. These compounds or their analogues could potentially be used in cancer-therapy strategies.     

Metastasis to the thyroid diagnosed by fine-needle aspiration biopsy

BACKGROUND: Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine-needle aspiration biopsy (FNAB) in any suspected case. DESIGN: A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre. PATIENTS: Twenty-two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years. RESULTS: Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru-cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work-up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis. CONCLUSIONS: Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general.     

Diabetes and prognosis in a breast cancer cohort

Purpose

Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics.

Methods

The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes.

Results

In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5?years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49?C2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31?C3.97).

Conclusion

In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5?years follow-up period.     

恶性肿瘤并发弓形虫感染的研究

本文采用间接血凝试验(IHA)方法,对75例恶性肿瘤患者,62例普通病人及正常人对照组75例,进行血清弓形虫抗体的检测,以效价≥1:64为阳性。结果表明,恶性肿瘤组感染率为33.3%,普通病人组感染率为11%(P<0.01),正常对照组感染率为5%以下(P<0.001)。以恶性葡萄胎患者感染率最高,达83%;其次为白血病及消化道肿瘤,分别为40%,39%,以上三种肿瘤患者的抗体滴度几何均数(GMT)分别为48.51,63.59和38.1。7例乳腺癌和11例肺癌患者抗体均为阴性。     

Breast cancer

Breast cancer remains a public-health issue on a global scale. We report new information about the disease from the past 5 years. Early age at first birth, increasing parity, and tamoxifen use are related to long-term lifetime reduction in breast-cancer risk. Ductal carcinomas in situ has been suggested to be renamed ductal intraepithelial neoplasia to emphasise its non-life-threatening nature. An alternative approach, the progenitor/stem cell theory, predicts that only some tumour cells cause cancer progression and that these should be targeted by treatment. Mammography and ultrasonography are still the most effective for women with non-dense and dense breast tissues, respectively. Additionally, MRI, lymphatic mapping, the nipple-sparing mastectomy, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant treatments are promising for subgroups of breast-cancer patients. Although tamoxifen can be offered for endocrine-responsive disease, aromatase inhibitors are increasingly used. Assessment of potential molecular targets is now important in primary diagnosis. Tyrosine-kinase inhibitors and other drugs with anti-angiogenesis properties are currently undergoing preclinical investigations.     

High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.