Present and future state of cancer screening for esophageal cancer and gastric cancer

Recently, endoscopic examinations have played a major role in the diagnosis and treatment in the field of gastroenterology. It is considered that endoscopy would be an important examination for cancer screening of the esophagus and the stomach. However, endoscopic services for cancer screening are in short supply. Furthermore, we have to take the complications and poor economic benefits of endoscopy in to consideration when we apply it as a practical cancer screening system. Thus, an effective primary screening system must be provided for the endoscopic screening of cancer of the esophagus and the stomach. People with a defect in aldehyde dehydrogenase-2(ALDH2)should be distinguished by their facial flushing in drinking and for their high risks of esophageal cancer. In cases with gastric cancer screening by endoscopy, an x-ray study is expected to be a primary screening because of its efficacy. It already has been recommended for population-based screening in Japanese guidelines for gastric cancer screening. In cases with opportunistic screening of gastric cancer, patients should be allowed to choose from several studies such as the x-ray study, direct endoscopy, and the so-called high risk screening of gastric cancer for estimating risks and planning of screening for gastric cancer.     

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.     

Preoperative cancer chemotherapy for gastric cancer

Preoperative cancer chemotherapy for gastric cancer was reviewed with special emphasis on histologic findings and survival. Preoperative chemotherapy with intravenous, split administration of MMC 40 mg caused considerable damage to "micro-solitary metastatic foci" in metastatic lymph nodes. In view of the lipid-adsorbing ability of the lymphatic stream, emulsified 5-FU was used orally in 182 patients with gastric cancer; histologic findings revealed that the emulsified 5-FU enhanced the antitumor efficacy for metastatic lymph nodes as well as the primary lesion. However, the 5-year survival rate for gastric cancer patients undergoing preoperative emulsified 5-FU therapy did not differ from the control, with only the exception of patients with Stage III gastric cancer. On the other hand, combined therapy involving preoperative intra-arterial infusion and surgery was carried out in 62 patients with gastric cancer. These preoperative treatments using MMC, 5-FU, VLB, MTX and/or cytosine arabinoside entailed continuous infusion for 15 to 20 hours; the histologic changes observed revealed marked antitumor effects on the primary focus as well as metastatic lymph nodes. The five-year survival rate for the 62 patients was compared with that for 99 patients with gastric cancer in the corresponding period. The survival rate was analyzed based on the degree of serosal invasion. The overall survivals in the 62 patients were higher than those in the controls for the first 3 years. At 4 to 5 years, the survival rates for both the treated and control groups were approximately equal. In patients without serosal invasion, the survival rates were higher in treated cases than in the controls for the first 2 years. Thirty-nine patients with serosal invasion had significantly higher survival rates than the controls for the first 3 years. The survival rates for the treated patients with cancerous infiltration of ther organs were about the same as those for the corresponding control patients.     

肺癌与食管癌术后乳糜胸的临床特点分析

目的探讨肺癌和食管癌切除及淋巴结清扫术后乳糜胸病例的临床特点。方法回顾性分析1203例肺癌术后9例乳糜胸患者和2361例食管癌术后34例乳糜胸患者的临床资料。结果肺癌组术后乳糜胸的发生率(0.8%)低于食管癌组(1.4%),并且临床症状及体征明显较食管癌组轻,保守治疗成功率高。所有患者痊愈出院。结论肺癌术后乳糜胸的发生率、病因、临床表现、诊断及治疗与食管癌术后乳糜胸有明显不同。     

Immunotherapy for head and neck cancer

Overall survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has not improved appreciably over the past few decades. Novel therapeutic approaches, such as immunotherapy, are under clinical investigation since the standard treatments are toxic and have not successfully controlled this disease with sufficiently high success rates. Cancer immunotherapy describes various techniques to expand and activate the immune system to control tumor growth in vivo, and clinical evaluation has so far demonstrated low toxicity. Immunotherapy appears to have the most applicability in settings of minimal residual disease and to reduce distant metastases after other therapeutic interventions, and its potential clinical value is now receiving intensive evaluation. Emerging forms of SCCHN immunotherapy involve both the use of monoclonal antibodies (mAb) that target growth factor receptors where immune activation appears to contribute to tumor cell lysis, as well as various forms of active vaccination strategies which activate and direct the patient’s cellular immunity against the tumor. This article reviews immunotherapeutic strategies currently in clinical trials or under development for patients with SCCHN.     

癌症治疗存在的问题以及生物治疗面临的机遇与挑战

随着生物医学理论与技术的进步，癌症的疗效有了明显的提高，但仍远不能令人满意，究其原因不仅在于缺乏高效的药物或技术，也应该反思我们对癌症的认识上是否存在误区，从而导致我们现行的癌症防治策略存在偏差。作者根据自身从事该领域研究的认识，就目前对于癌细胞的生物学     

Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes

Background:

Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early.

Methods:

Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass.

Results:

Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05).

Conclusion:

Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.     

Completeness of pedigree and family cancer history for ovarian cancer patients

Objective

To investigate the completeness of pedigree and of number of pedigree analysis to know the acceptable familial history in Korean women with ovarian cancer.

Methods

Interview was conducted in 50 ovarian cancer patients for obtaining familial history three times over the 6 weeks. The completeness of pedigree is estimated in terms of familial history of disease (cancer), health status (health living, disease and death), and onset age of disease and death.

Results

The completion of pedigree was 79.3, 85.1, and 85.6% at the 1st, 2nd, and 3rd time of interview and the time for pedigree analysis was 34.3, 10.8, and 3.1 minutes, respectively. The factors limiting pedigree analysis were as follows: out of contact with their relatives (38%), no living ancestors who know the family history (34%), dispersed family member because of the Korean War (16%), unknown cause of death (12%), reluctance to ask medical history of relatives (10%), and concealing their ovarian cancer (10%). The percentage of cancers revealed in 1st (2%) and 2nd degree (8%) relatives were increasing through surveys, especially colorectal cancer related with Lynch syndrome (4%).

Conclusion

Analysis of pedigree at least two times is acceptable in Korean woman with ovarian cancer from the first study. The completion of pedigree is increasing, while time to take family history is decreasing during three time survey.     

Radiotherapy and TRAIL for cancer therapy

The use of radiotherapy and concomitant chemotherapy substantially improved cure rates in patients with different malignant tumours. However, it is unlikely that further improvements based on conventional chemotherapy may be achieved in the future since increased rates of acute side effects already limit the value of these approaches. Additionally, the increased local control rates are counterweighted by still high rates of distant failures resulting in low net gains for the patients. Thus, there is a currently unmet need for the integration of target-specific drugs improving local control as well distant control into radiation based treatment protocols. In this regard, the death-receptor ligand TNF-α-related apoptosis-inducing ligand (TRAIL/Apo2L) and TRAIL-receptor agonistic antibodies were shown to display a high selectivity for tumour cells and act synergistically with conventional chemotherapy drugs and radiation. Up to now it has been shown that radiation strongly sensitises malignant cells to TRAIL and TRAIL-agonistic antibodies. Synergistic induction of apoptosis was demonstrated in a majority of malignant cell types and xenograft models. Especially in those cells types displaying only weak responses to either treatment alone, strong sensitising effects were described. Moreover, in merely all normal cells and tissues no synergistic effects were found. Depending on cell type and experimental setting, the efficacy of combined treatment is determined by the p53-status, the balance between pro- and anti-apoptotic Bcl-2 proteins and modulation of TRAIL-receptor signal transduction.     

靶向肿瘤干细胞治疗肿瘤

具有独特的分子表达、表面标志物、干性相关信号通路和代谢模式等方面特征的肿瘤干细胞（cancer stem cell, CSC） 因其具有高致瘤、高转移、高治疗抵抗能力,可能是多种类型恶性肿瘤生长、转移、治疗抵抗的关键因素,也是肿瘤发生和复发的 重要根源。正常干细胞在产生了第一个致癌突变之后将逐步发展成为癌前干细胞和CSC,随后在突变和微环境的共同作用下进 一步积累突变增加异质性,并与CSC可塑性转变交织在一起推动肿瘤的发生和进展,促进肿瘤的复发、转移及治疗抵抗。为了更 好地治疗肿瘤,现已研发了多种类型的靶向CSC的治疗策略,包括靶向CSC的细胞表面标志物、信号转导途径、微环境、代谢模式 等,以及促CSC分化、靶向CSC的免疫治疗等其他策略。多个靶向CSC治疗肿瘤的新药在临床试验中已经展现出良好的治疗效 果,然而,也有一些抗肿瘤新药的失败为未来研发提供了值得注意的教训。未来肿瘤治疗中,特异地靶向患者肿瘤中所有异质性 的CSC,并同时清除癌前干细胞和子代肿瘤细胞,将会更好地抑制肿瘤生长、转移和复发,从而为治愈肿瘤带来新的希望。     

凋亡与肿瘤靶向治疗

凋亡异常与肿瘤发生密切相关.由于凋亡过程受基因调控,所以肿瘤对靶向凋亡调控基因的治疗是敏感的.一种靶向凋亡治疗肿瘤的策略已经形成,方法包括通过活化肿瘤细胞内的凋亡分子和引入外源性促凋亡分子直接诱导凋亡;通过阻断生存信号的传导间接诱导凋亡.     

Complementary and alternative therapies for cancer

Many cancer patients use therapies promoted as literal alternatives to conventional medical care. Such "alternative" modalities are unproven or were studied and found worthless. These can be harmful. An even greater proportion of cancer patients uses "complementary" therapies along with mainstream cancer treatment. Most are helpful adjunctive approaches that control symptoms and enhance quality of life. This review describes alternative as well as complementary therapies commonly used today by cancer patients. Herbal remedies also are discussed. Evidence regarding the efficacy and safety of complementary/alternative medicine (CAM) is reviewed, and implications for oncologists are discussed. To encourage open communication of CAM use by patients, oncologists should be knowledgeable about the most popular remedies and know where to find reliable information for themselves and for their patients.     

Chemotherapy and radiotherapy for urological cancer

Prostate cancer, bladder cancer, renal cancer and testicular cancer are common among urological cancers. The treatment strategy for testicular cancer using chemotherapy has been well established and has been shown to be successful. Chemotherapy and radiotherapy play important roles in multidisciplinary therapy for bladder cancer. Radiotherapy is often used as a radical treatment that is practically equivalent to surgery for prostate cancer. In addition, radiotherapy is useful in cases of bone or brain metastases. In the field of chemotherapy, the development of new agents that would make breakthroughs similar to that of cisplatin is awaited. Taxanes and gemcitabine are good candidates. In the field of radiotherapy, 3D conformal radiation therapy (CRT), which has excellent beam distribution, has recently come into wide use. Moreover, brachytherapy and proton and ion beam therapy are expected to prove useful in prostate cancer therapy.     

Radiotherapy for head and neck cancer

The length and quality of head and neck cancer survivorship continues to improve. Radiotherapy has been central to this process through advances in treatment technology, fractionation schemas, radiosensitizing chemotherapy, and surgical technique. The future of head and neck radiotherapy looks brighter still with progress in radiosensitizing biologic therapy, molecular characterization, functional imaging, and rehabilitative strategies fast approaching. Head and neck cancer, a disease once fraught with nihilism and failure, is evolving into a major success story of multidisciplinary solid tumor management. Continued dedication and work on the part of provider and patient alike will be required to make this promise a reality.     

Chemo-radiotherapy for head and neck cancer

Many randomized trials have investigated the effect on survival of induction chemotherapy; none however, has demonstrated improved survival. A study of the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated the feasibility of induction CDDP/5-FU plus surgical salvage as an alternative to initial laryngectomy, but it did not include a radiation-alone treatment arm. Thus, a three-arm trial (R 91-11) was needed to compare the regimen of induction chemotherapy plus surgical salvage treatment with radiation alone and with concurrent chemo-radiation, to determine whether the addition of chemotherapy led to better results than conventional radiation alone. R 91-11 data revealed that concurrent chemo-radiation significantly increased the time to laryngectomy and chemotherapy suppressed distant metastasis, but there was no difference in overall survival. Single-agent docetaxel is known to induce a response in 22-45% of patients with recurrent squamous cell cancer of the head and neck. When used in combination with CDDP, response rates of between 40 and 54% have been reported. Increased expression the epidermal growth factor receptor (EGFR) is reported in head and neck cancer. Anti-EGFR monoclonal antibody is associated with decreased cell proliferation, inhibition of metastasis and angiogenesis, and it has a synergistic effect with chemotherapy or radiotherapy. It is hoped that further advances will lead to greater realization of the therapeutic potential of these compounds as anticancer agents.     

The importance of bone management for cancer bone disease--positioning of zoledronic acid for multiple myeloma, genitor-urinary cancers (renal cancer and prostate cancer), lung cancer and breast cancer

With the advances in early diagnosis and treatment of cancer, prognosis of cancer patients has been improved significantly. Therefore improvement of QOL for cancer patients has become an important issue. Prevention of skeletal related event is one of the major factors to improve QOL in patients with bone metastasis. Since the clinical introduction of zoledronic acid, management of bone lesions has been improved and decreased SRE significantly. The specialists from four disease area which is multiple myeloma, urological cancer, lung cancer and breast cancer have discussed the benefits (and risks?) of the zoledronic acid with the current status of bone management in each cancer.