The impact of nutrition in urogenital cancers

Prostate, bladder and kidney cancers remain the most common cancers of the urinary tract. Despite improved primary prevention, detection and treatment, the incidence of age-related cancers of the urinary tract is likely to rise as a result of global population ageing. An association of diet with prostate, bladder and kidney carcinogenesis is plausible since the majority of metabolites, including carcinogens, are excreted through the urinary tract. Moreover, large regional differences in incidence rates of urologic tumours exist throughout the world. These rates change when people relocate to different geographic areas, which is suggestive of a strong environmental influence. As a result of these observations, numerous studies have been conducted to assess the effects of diet and nutritional status in kidney, bladder and prostate carcinogenesis. Here, we review the literature assessing the effect of diet and nutritional status on urological cancer risk, which has attracted the most interest.     

Chromosome instability in lymphocytes from two patients affected by three sequential primary cancers: the role of fragile sites

The chromosomal aberration rate and the expression of fragile sites induced by aphidicolin were evaluated in metaphase chromosomes obtained from peripheral blood lymphocytes of two untreated patients with multiple primary cancers. Spontaneous aberrations of chromosome number and structure and chromosome fragility were compared with controls with the use of the same methods. Chromosomal aberration rates and expression frequencies of fragile sites were significantly higher in the patients than in normal control subjects. In the patients, all but one structural chromosome aberration involved at least one fragile site. Our results suggest that fragile sites may be unstable regions of the human genome, which might play an important role in the genetic instability associated with cancer predisposition.     

The risk of contralateral breast cancer in daughters of women with and without breast cancer

We aimed to estimate the 15‐year and lifetime risks of contralateral breast cancer in breast cancer patients according to the age of diagnosis of the first cancer and the history of breast cancer in the mother. The risks of contralateral breast cancer were estimated for all 78,775 breast cancer patients in the Swedish Family‐Cancer Database (age at diagnosis of first breast cancer <70 years). The risk of experiencing a contralateral breast cancer within 15 years of diagnosis was 8.4% [95% confidence interval (CI): 8.1–8.7%] for women with an unaffected mother, was 12% (95%CI: 11–13%) for a woman with a mother with unilateral breast cancer and was 13% (95%CI: 9.5–17%) for women with a mother with bilateral breast cancer. In early‐onset diagnosed women (<50 years) with an unaffected mother, the risk of contralateral breast cancer until age 80 was 23% (95%CI: 20–26%) and for late‐onset (50–69 years) diagnosed women it was 17% (95%CI: 14–21%). In a woman with a mother with an early‐onset unilateral breast cancer, risk of contralateral breast cancer by age 80 was 35% (95%CI: 25–46%). Women with a mother with early‐onset bilateral breast cancer had 31% (95%CI: 12–67%) lifetime risk of contralateral breast cancer. The risk of contralateral breast cancer is higher for daughters of breast cancer patients than for daughters of women without breast cancer. Maternal cancer history and age at onset of first breast cancer in women should be taken into account when counseling breast cancer patients about their risk of contralateral breast cancer.     

A computer model for the study of breast cancer

A computer model was designed as a relational database to assess breast cancer screening in a cohort of women where the growth and development of breast cancer originates with the first malignant cell. The concepts of thresholds for growth, axillary spread, and distant sites are integrated. With tumor diagnosis, staging was performed that includes clinical and sub-clinical states. The model was parameterized to have staging characteristics similar to data published by the Surveillance, Epidemiology, and End-Results (SEER) Program. Validation was accomplished by comparing simulated staging results with non-SEER sources, and simulated survival with independent clinical survival data.     

Family attitudes in youth as a possible precursor of cancer among physicians: A search for explanatory mechanisms

A measure of youthful family attitudes, the Closeness to Parents Scale, has continued to be predictive of cancer among physicians in a prospective study of medical students. Nonetheless, questions have remained concerning the meaning and reliability of this measure and whether its predictive value is diminishing over time. Perhaps more important, it is necessary to ascertain whether the relationship is the result of some methodological artifact or whether it is mediated by an association with known risk factors, such as smoking, drinking, and radiation exposure. Each of these issues was examined in turn, using a variety of statistical techniques to refine the scale and to equate cancer and control groups with respect to risk factors as well as possible artifacts. In a group of 913 men, it was found that the scale is primarily a function of good father-son relationships and that its association with later cancer persists even after the influence of possible mediating and artifactual variables is statistically controlled. Several possible explanations for these findings are discussed.This work was supported by National Cancer Institute Grant 1 R18 CA24416-02, National Institute on Aging Grant 1 RO1 GM25822-01, and The Johns Hopkins University.     

Surgical outcome of synchronous second primary cancer in patients with gastric cancer

PURPOSE: In order to improve the likelihood of curative and safe gastric surgery, this study investigated the clinical features and surgical outcomes of gastric cancer with a synchronous cancer. PATIENTS AND METHODS: The clinicopathological data of 10,090 gastric cancer patients at Samsung Medical Center from September 1994 to December 2006 were retrospectively analyzed. Of them, 90 patients with gastric cancer and a synchronous second primary cancer underwent simultaneous surgery for gastric cancer and second primary cancer. The clinicopathological characteristics of the patients, surgical outcome, and prognosis were examined. RESULTS: The most common synchronous second primary cancer was colorectal cancer (37 patients), followed by hepatocellular carcinoma (13 patients), renal cell carcinoma (11 patients), and pancreatic carcinoma (5 patients). The incidence of a second primary cancer in the gastric cancer patients was higher than the incidence in the general population. Stage I gastric cancer patients had more synchronous cancers than stage II patients (59 vs. 31). Postoperative complications were encountered in 7 patients. Four patients underwent reoperation. Two patients died from hepatic failure and leakage of esophagojejunal anastomosis. The 5-year survival rate of stage I and II gastric cancer was 61% and 39%, respectively. CONCLUSION: Since gastric cancer patients with a synchronous second primary cancer are not rare, the possibility of synchronous cancers in gastric cancer patients should be considered. The prognosis of early stage gastric cancer patients with a synchronous second primary cancer was influenced more by the presence of the second primary cancer than by the gastric cancer itself.     

Natural killing activity is associated with progression of gastric cancer

Previously, we proposed a new analysis of natural killing activity, in which an individual effector/target cell ratio was employed for comparison according to the peripheral number of effector cells. In 51 patients with gastric cancer, the activity was studied using that modified analysis. Natural killing activity was activated in patients with early cancer, where tumor-cell invasion was restricted to the mucosa or the submucosa, even though in well-differentiated adenocarcinoma with invasion of the mucosa alone, the activity remained at the level of controls. In contrast, the activity in advanced cancer, where tumor cells infiltrated beyond the submucosa, came to be inactivated as the cancer progressed. These facts suggest that natural killing activity in patients with gastric cancer is closely associated with tumor invasion and that reactive activation of the activity against tumor is induced, at least, in some patients with early stage.     

Analysis of clinicopathological features and prognosis of 1315 cases in colorectal cancer located at different anatomical subsites

PurposeCompare and analyze the clinicopathological features and prognosis of 1315 patients with colorectal cancer located at different anatomical subsites.MethodsA retrospective study was conducted to analyze the clinicopathological features and prognosis from 1315 patients with colorectal cancer who underwent surgery in the department of gastrointestinal surgery at the Second Affiliated Hospital of Dalian Medical University from January 2013 to January 2019. Among them, 287 patients were divided into the right-sided colon cancer (RCC) group; 329 patients were included into the left-sided colon cancer (LCC) group and the remaining 699 patients were assigned to the rectal cancer (RC) group. Clinicopathological features such as gender, age, pathological differentiation, neurovascular invasion, TNM stage, related tumor markers, maximum tumor diameter (MTD), median survival time and overall survival rate were extracted and analyzed.ResultsPatients in the RCC group had the oldest age of onset, highest positive rate of serum CA199 and greatest number of poorly differentiated adenocarcinomas among the three groups and significant statistical differences were found. The RC group had the highest positive rate of vascular invasion (42.9%) and the greatest number of patients in stage I and IV (19% and 3.9%, respectively). Besides, the number of patients with stage T1-T2 adenocarcinoma in RC group was also the highest among the three groups. There were no significant differences in gender, perineural invasion as well as serum levels of CEA, CA724 and CA242. The median survival time of RCC, LCC and RC were 72, 70 and 73 months, respectively, with significant inter-group differences (P = 0.049).ConclusionThe age of onset of right-sided colon cancer is the oldest on average and poorly differentiated tumors accounted for the highest proportion. Besides, average maximum tumor diameter is the largest in right-sided colon cancer. In terms of median survival time, LCC is worse than RCC and RC. Colorectal cancer at different anatomical subsites has different epidemiological, clinicopathological features and prognosis. Fully understanding the clinicopathological features of colorectal cancer at different anatomical subsites is of certain guiding significance for the clinical diagnosis and treatment of colorectal cancer, and is conducive to individualized treatment and accurate treatment.     

Estrogen and cancers of the colorectum,breast, and lung in postmenopausal women

As estrogens play an important role in maintaining physiological function in various organs, the estrogen decrease after menopause is thought to cause various diseases frequently observed in postmenopausal or elderly women. With the aging of society and a decrease in infectious or vascular diseases, neoplasms have now become the most frequent cause of death in Japan. Cancers of the colorectum, breast, and lung have been rapidly increasing both in incidence and death, especially among postmenopausal women. Interestingly, all three of these cancers are associated with estrogens. In premenopausal women, ovarian estrogens plays major roles in the female reproductive organs through the classic estrogen receptor, ER‐α. In postmenopausal women, however, estrogens produced/activated by peripherally localized estrogen‐metabolizing enzymes such as aromatase, which converts androgen into estrogens, are thought to play physiologically and pathobiologically important roles in various organs through second ER, namely ER‐β, distributing systemically. In this article, the association of estrogens with these cancers in postmenopausal or elderly women are reviewed, especially focusing on the role of ER‐β and peripheral estrogen metabolism. The possibility of prevention or treatment of these diseases through estrogenic control is also discussed.     

Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers

Family history-based risk assessment (FHRA) is a genetic tool for identifying those at risk of disease. Genome-wide association studies have shown that single nucleotide polymorphisms (SNP) are statistically associated with low- to moderate-level risks of diseases. There has been limited study of complementarity for these two assessment methods. We sought to compare cancer risk categorizations from FHRA and from Navigenics Personal Genome Screening (PGS). We compared FHRA with PGS for breast (22 females), prostate (22 males), and colon cancer (44 males and females) assessed by kappa (κ) statistic. We also assessed each participant's hereditary risk based on clinical criteria and/or gene-test results. Both FHRA and PGS placed 59%, 68% and 44% of participants into the same risk categories for breast, prostate, and colon cancer, respectively. Overall, however, there was little concordance in FHRA versus PGS for all three cancer risks (κ<0.2). FHRA assigned 22 with hereditary risk compared with PGS, which identified one as high risk (P<0.0001). We assessed nine with hereditary colorectal cancer risk, five with germline mutations, but none were classified as PGS high risk (P=0.0001). FHRA and PGS may be complementary tools for cancer risk assessment. However, evaluation of family history remains the standard to evaluate an individual's cancer risk until further research.     

Increased incidence of malignancy in patients with primary hyperparathyroidism

Background/aimPrimary hyperparathyroidism (PHPT) is a disease that is diagnosed more frequently and generally in the asymptomatic period, with widely available biochemical tests. Evidence suggesting an association between PHPT and malignancy risk is increasing. Clarification of this association will be useful in PHPT for malignancy screening and management of patients with PHPT. In this study, we aimed to investigate the frequency of cancer in PHPT patients.Materials and methodsA total of 775 PHPT patients were included in the retrospective study. Demographic, clinical and laboratory data of the patients were evaluated retrospectively.ResultsMalignancy was detected in 128 (16.50%) of 775 PHPT patients (female/male: 625/150). The mean age at diagnosis of PHPT was 57.99 ± 10.86 years, and the mean age at diagnosis of malignancy was 57.46 ± 11.17 years. Of the 128 patients with malignancy, 53 (41.40%) were diagnosed in the same year as PHPT. In terms of malignancy types, 51 (6.50%) of 775 PHPT patients had thyroid cancer. Thyroid cancer was followed by breast cancer (2.30%) and stomach cancer (1%) in order of frequency.ConclusionWe think that PHPT patients should be examined more carefully in terms of cancer risk, especially thyroid cancer. More comprehensive studies are needed to clarify the relationship between PHPT and cancer.     

Trans-arterial hepatic radioembolisation of yttrium-90 microspheres

The liver represents a frequent site for metastatic disease, in addition to being a site for primary cancer. Hepatic metastases from certain neoplasms, such as colon, neuroendocrine, melanoma and gastrointestinal stromal tumour have a distinct predilection to metastasize the liver, which in many cases may represent the only or the dominant site of disease. In these circumstances, cytoreduction via surgery or in situ ablative techniques aims to influence the natural history of the disease progression and improve clinical outcomes.Liver directed therapy utilising yttrium-90 microspheres represents a recently introduced in situ multidisciplinary cancer therapy that has caught the attention of many physicians faced with the challenges of treating these complex patients. Although similar to other forms of trans-arterial liver directed therapy, there are discrete differences and potentially fatal treatment consequences unique to this therapy. This objective of this review article is to provide the reader a basis for understanding the therapeutic principles, patient exclusion criteria, pre and post therapy investigations and salient clinical results in the two most commonly treated disease types; metastatic colorectal cancer and hepatocellular cancer.     

良、恶性肝病、卵巢疾病和胰腺疾病患者血清AFP、CEA、CA125和CA199水平的相关研究

目的:血清中AFP、CEA、CA125和CA199的测定研究良、恶性肝病、卵巢疾病和胰腺疾病诊断的临床意义.方法:发光免疫分析测定了52例正常对照组,68例良性肝病,65例肝癌,56例卵巢疾病和51例胰腺疾病的血清中AFP、CEA、CA125和CA199水平,批内CV＜5%,批间CV＜10%.结果:良性疾病患者的血清四项肿瘤标记物水平大致与对照组的相似(p＞0.05).原发性和继发性肝癌患者的血清CA125和CA199水平较对照组显著升高(p＜0.001).卵巢癌与胰腺癌患者也同样如此(0.001＜p＜0.05).结论:血清AFP、CEA、CA125和 CA199的联合测定是诊断和鉴别肝癌、卵巢癌和胰腺癌的最好方法.     

The genetic era of childhood cancer: Identification of high-risk patients and germline sequencing approaches

Childhood cancer is a leading cause of death by disease in children ages 5–14, for which there are no preventive strategies. Due to early-age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown. Several efforts have been made to develop tools to identify children with increased risk of cancer who may benefit from genetic testing but their validation and application on a large scale is necessary. Research on genetic bases of childhood cancer is ongoing, in which several approaches for the identification of genetic variants related to cancer predisposition have been used. In this paper, we discuss the updated efforts, strategies, molecular mechanisms and clinical implications for germline predisposition gene alterations and the characterization of risk variants in childhood cancer.     

Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients

There is strong evidence that overtly inactivating mutations in RAD51C predispose to hereditary breast and ovarian cancer but the prevalence of such mutations, and whether they are associated with a particular clinical phenotype, remains unclear. Resolving these questions has important implications for the implementation of RAD51C into routine clinical genetic testing. Consequently, we have performed a large RAD51C mutation screen of hereditary breast and ovarian cancer families, and the first study of unselected patients diagnosed with ovarian cancer. Our data confirm a consistent but low frequency (2/335 families) of inactivating RAD51C mutations among families with a history of both breast and ovarian cancer and an absence of mutations among breast cancer only families (0/1,053 families). Our data also provide support for the designation of the missense variant p.Gly264Ser as a moderate penetrance allele.     

表皮生长因子（EGF）放射免疫分析方法建立及临床应用

目的：研究表皮生长因子（epidermal growth factor,EGF）放射免疫分析方法的建立和临床应用。方法：采用人EGF对豚鼠免疫,获得高比度的抗血清,建立了体外放射免疫分析,并用来检测正常人、肝癌、糖尿病、结肠癌、肺癌、胃癌、子宫肌瘤及卵巢癌患者血清EGF浓度。结果：标准曲线范围（0.2～27）ng/ml;批内和批间（CV）分别为4.6%及8.7%;灵敏度为0.18ng/ml;回收率在95%～104%之间。分别测定正常人、肝癌、糖尿病、结肠癌、肺癌、胃癌、子宫肌瘤及卵巢癌血清EGF浓度,依次为（0.52±0.25）ng/ml,n=74;（1.29±0.58）ng/ml,n=99;（1.91±0.58）ng/ml,n=90;（1.43±0.56）ng/ml,n=90;（1.30±0.47）ng/ml,n=95;（1.25±0.58）ng/ml,n=87;（1.49±0.46）ng/ml,n=44;（1.79±0.60）ng/ml,n=54。病人血清EGF浓度与正常人经统计学处理均P〈0.01,有显著性差异。结论：所建立的EGFRIA能用于临床及科研需要。     

肿瘤干细胞的研究现状

传统理论认为肿瘤生长是所有肿瘤细胞一起增殖的结果,因而治疗方法主要是针对肿瘤组织内的大多数细胞,常有复发和转移,使治疗失败。肿瘤干细胞的提出,可靶向性杀伤肿瘤干细胞从而使根治肿瘤和防止肿瘤复发和转移成为可能,且先前诸多关于肿瘤发生发展机制、细胞信号途径等研究成果可能需要重新评价,对传统的肿瘤治疗方式提出了巨大挑战。就肿瘤干细胞的起源、存在证据、肿瘤干细胞与正常干细胞之间关系、临床意义及展望综述如下。