Hereditary cancer]

A significant proportion of all cancers is inherited or develops in genetically susceptible individuals. An updated overview and tabulations are given on inherited cancer, including the monogenic cancer syndromes, cancer caused mainly by predisposition in heterozygous carriers for autosomal recessive syndromes, and the same of different types of cancers occurring in families exhibiting irregular autosomal dominant inheritance. Environmental factors act in concert with genetically susceptible genes to cause cancer. A mechanism for the initiation and progression of cancer on the cellular level is outlined. The identification of an ever-increasing number of cancer-susceptible genes enables the development of new genetic tests. Some advantages and problems associated with predictive genetic testing for cancer are discussed.     

青年结直肠癌分析

目的:探讨青年结直肠癌的临床特征.方法:收集48例35岁以下的结直肠癌病例临床资料并进行系统性分析.结果:青年人结直肠癌主要临床表现为粘液血便或便血、腹痛、大便习惯改变,肿瘤主要在直肠及乙状结肠,组织学类型以分化不良为主,Duke's分期以C、D期为主,根治率43.75%,5年生存率为28.21%.结论:青年结直肠癌临床症状不典型,恶性程度高,手术根治率低,预后差.早期诊断,早期治疗是提高生存率的关键.     

Physical activity and colon cancer

Heart disease and cancer, the major causes of mortality and morbidity in Western countries, have common risk factors. Exercise appears to reduce the risk of cardiovascular disease, but its role with respect to primary prevention of cancer has not been emphasized. Here we evaluate the epidemiological studies dealing with exercise and colon cancer. Despite the fact that different methods of assessing the amount of typical exercise of individuals and the different types of physical activity measured (occupational and recreational), there is remarkably consistent evidence that people who are highly physically active could be at a reduced risk of cancer of the colon. An analysis of case-control and cohort studies suggests that exercise might reduce the risk, at least in men, by up to one-third. We conclude that exercise has been overlooked as a potentially useful, effective, and acceptable method for reducing the risk of colon cancer.     

Nutritional factors and colon cancer

During the last 2 decades, substantial progress has been made in understanding the relationship between dietary constituents and the development of colon cancer in man. Unlike studies of cancer among smokers and nonsmokers, nutritional epidemiologic studies are confronted with the inherent difficulty of assessing reasonably precise exposures. The lack of consistency between international correlation studies and case-control studies does not necessarily negate a dietary etiology of colon cancer because these inconsistencies may have arisen, at least in part, from methodological limitations. Some of these deficiencies in epidemiological studies of diet and cancer have been corrected; recent case-control studies demonstrated that high dietary fat is a risk factor for colon cancer development and that an overall increase in intake of foods high in fiber might decrease the risk for colon cancer. The results of epidemiologic studies may be assumed to present conservative estimates of the true risk for cancer associated with diet. The populations with high incidences of colon cancer are characterized by high consumption of dietary fat, which may be a risk factor in the absence of factors that are protective, such as whole-grain cereals and of other high fiber. Laboratory-animal model studies have shown that certain dietary lipids and fibers influence tumorigenesis in the colon. The data of metabolic epidemiological and laboratory-animal model studies are sufficiently convincing with respect to the enhancement of colon cancer by type of fat and protection by certain dietary fibers.     

Gene therapy for colon cancer

The enormous number of newly diagnosed cases of colorectal cancer that occur each year and the lack of agents that are highly effective for all patients underscore the need for novel approaches to combating the disease. Gene therapy as a developing treatment modality is already well established, with a number of trials ongoing and a vast range of other approaches being assessed in animal and cell culture experiments. In this brief review, we have discussed five gene therapy trials in colon carcinoma that are ongoing or in the approval process in the United States. The gene therapy approaches being employed can be divided into three major categories: (1) enzyme/prodrug systems (HSVtk/ganciclovir; CD/5-fluorocytosine); (2) tumor suppressor gene replacement therapy with wild-type p53; and (3) immune-gene therapy which is based on cytokine or tumor antigen expression to induce tumor immunity (e.g., CEA). Replication-deficient recombinant adenoviral vectors are predominantly used for colon cancer gene therapy, because they can be produced at high titer and they readily infect a number of different cell types. One trial uses polynucleotide therapy for antitumor immunization with intramuscular injection. All of these studies are phase I trials, principally designed to evaluate safety, but they will also provide data on gene delivery. Some trials may provide some insight into potential therapeutic effects. We have alluded to some of the concerns on toxicity related to the use of adenovirus, risks and side effects from transgenes, lack of tumor-specificity of transgene expression, and potential problems with efficient gene delivery to solid tumors. The clinical trials, however, will provide insight that will inform design of future studies with respect to dose, form, and frequency of administration, as well as to the value of biologic and clinical endpoints. The molecular analysis of the fundamental basis of colon cancer has moved at a remarkable pace and that progress seems set to continue. Thus, the basic foundations for gene therapy are undoubtedly in place: a clinical need; growing understanding of basic tumor biology; and ever-improving delivery systems. The field is at a very early stage in its evolution, and one concern is that the considerable hurdles that must be overcome are seen as examples of the failure of cancer gene therapy; however, we believe these challenges will be overcome. The authors also believe that colon cancer gene therapy is likely to take new directions, such as use as adjuvant to radical surgery, rather than attempts to treat end-stage disease when the liver is replaced by metastases. Other new directions might include prophylactic gene-based immunization against a panel of well-characterized tumor antigens, at least for persons shown to be at high risk of colon cancer because of genetic or other predisposition. A marriage between gene therapy approaches and conventional anticancer treatments such as radiotherapy and chemotherapy also seems likely. There is already evidence of this move with demonstration of synergism between p53 replacement and radiotherapy and chemotherapy. It is also likely that therapies will be developed that combine elements from the cancer gene therapies discussed previously, namely, suicide gene transfer, immune modulation, and modulation of defective cancer genes. Perhaps one of the main concerns is not that researchers in cancer gene therapy want to walk before they can run, but that the public and government agencies believe they can. The next 10 years will be an interesting time in the development of novel treatments against colon cancer.     

Cell adhesion molecules and colon cancer

There is a general consensus that cell-cell and cell-matrix interactions determine, at least in part, the behaviour of colon cancer. The biological mediators responsible for these interactions are cell adhesion molecules belonging to several major receptor families called integrins, cadherins, the immunoglobulin superfamily, hyaluronate receptors and mucins. Emerging data indicate that certain patterns of adhesion receptor expression are associated with more aggressive disease. The present review examines the role of each of the receptor families in the development and progression of large bowel cancer.     

Surgical standards in primary colon cancer

The surgical standards in the treatment of primary cancer of the colon include the radical resection of the tumor-bearing colon with truncal ligation of its vessels. Eradication of the tumor with complete dissection of the lymphatic drainage area increases the chance for cure (R0). The lymphatic dissection determines the extent of colonic resection: right hemicolectomy (ileo-transversostomy) with truncal ligation of the iliocolic and right colonic arteries for carcinomas of the cecum and ascending colon; transverse colectomy (ascendo-descendostomy) with ligation of the middle colic artery for carcinomas in the middle of the transverse colon; left hemicolectomy (transverso-rectostomy) with ligation of the inferior mesenteric artery at the aorta for cancer of the descending and sigmoid colon; extended sigmoid resection (descendo-rectostomy) with central lymphadenectomy and ligation of the inferior mesenteric artery distal to the left colic artery for cancer of the distal sigmoid colon. Carcinomas located in between two drainage areas (lateral transverse colon, hepatic or splenic flexure) are treated by extended hemicolectomies or subtotal colectomies with dissection of two lymphatic drainage areas. The monobloc no-touch isolation technique requires the ligation of vessels prior to the mobilisation of the colon. Exceptions from these standard operations (limited resections) are necessary for metastatic disease or in the acute emergency situation of perforation or obstruction. Application of these surgical principles will ensure the best possible treatment results in primary colonic cancer.     

Adjuvant systemic chemotherapy in colon cancer

The prognosis for patients with cancer of the colon is dubious. An intendedly curative colon resection is performed in two-thirds of these patients, but half of them will subsequently die from metastatic disease. Randomized trials of adjuvant therapy with fluorouracil in combination with levamisole or leucovorin have shown significant benefit in terms of increased disease-free survival and overall survival. In 1990 adjuvant treatment was recommended as routine therapy in high risk patients in USA. A number of European countries are routinely treating high risk patients with Dukes' C coloncarcinoma. The recommendations are based on results from several cooperative trials reviewed in this article. Treatment related toxicity accelerates with increasing age but was acceptable in the reviewed trials. Adjuvant therapy is widely accepted as an important supplement to surgery in high risk patients. A Conference on the results and experiences now available should take place in the near future in order to establish a national consensus on adjuvant chemotherapy in Denmark. Patients with resected Dukes' C coloncarcinoma should receive adjuvant chemotherapy including 5-fluorouracil and leucovorin. Randomized trials are needed to establish the most effective regimens but "no-treatment" controls are no longer ethically acceptable.     

Enhancement of experimental colon cancer by genistein

Several phytochemicals and micronutrients that are present in fruits and vegetables are known to exert cancer chemopreventive effects in several organs, including the colon. Among them, the soybean isoflavonoid genistein received much attention due to its potential anticarcinogenic, antiproliferative effects and its potential role in several signal transduction pathways. The present study was designed to investigate the effect of genistein on azoxymethane (AOM)-induced colon carcinogenesis and to study its modulatory role on the levels of activity of 8-isoprostane, cyclooxygenase (COX), and 15-hydroxyprostaglandin F2alpha dehydrogenase (15-PGDH) in the colonic mucosa and colon tumors of male F344 rats. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or a diet containing 250 ppm genistein. Beginning 2 weeks later, all animals except those in the vehicle-treated groups were given weekly s.c. injections of AOM (15 mg/kg body weight) for 2 successive weeks. All rats were continued on their respective dietary regimen for 52 weeks after AOM treatment and were then sacrificed. Colon tumors were evaluated histopathologically. Colonic mucosae and tumors were analyzed for COX, 15-PGDH, and 8-isoprostane levels. Administration of genistein significantly increased noninvasive and total adenocarcinoma multiplicity (P < 0.01) in the colon, compared to the control diet, but it had no effect on the colon adenocarcinoma incidence nor on the multiplicity of invasive adenocarcinoma (P > 0.05). Also, genistein significantly inhibited the 15-PGDH activity (>35%) and levels of 8-iosoprostane (50%) in colonic mucosa and in tumors. In contrast, genistein had no significant effect on the COX synthetic activity, as measured by the rate of formation of prostaglandins and thromboxane B2 from [14C]arachidonic acid. The results of this investigation emphasize that the biological effects of genistein may be organ specific, inhibiting cancer development in some sites yet showing no effect or an enhancing effect on the tumorigenesis at other sites, such as the colon. The inhibition of 8-isoprostane levels by genistein indicates its possible antioxidant potential, which is independent of the observed colon tumor enhancement, yet this agent may also possess several biological effects that overshadow its antioxidant potential. The exact mechanism(s) of colon tumor enhancement by genistein remain to be elucidated; it is likely that its colon tumor-enhancing effects may, at least in part, be related to inhibition of prostaglandin catabolic enzyme activities.     

Dietary factors and prevention of colon cancer

We are interested in the influence of trabeculectomy (TE) with releasable sutures to corneal curvature in the early postoperative period. 35 eyes of 31 patients were followed after operation. Corneal topography was made on the Topograph Opticon 2000 one day before, 1st day, 1st week, 1st month and during 6-12 months after operation. Astigmatism after operations was the highest on 1st day +3.7 D, which means elevation of about +2.8 D. During 1st month postoperative astigmatism was decreased by about 2.0 D, it is about +0.8 D more than before operation. During 6-12 months after operation temporary astigmatism nearly disappears, it only makes +0.25 D. The axis of astigmatism was without larger alterations. Small temporary changes were seen according to the place of TE. Temporary astigmatism was observed immediately after the extraction of the releasable sutures. Astigmatism after operation was influenced by the rate of filtration during the short postoperative time and also after extraction of the releasable suture.     

Hereditary colon cancers can be tiny: a cautionary case report of the results of colonoscopic surveillance

This case report describes a 45-yr-old woman with a strong family history of colorectal cancer who was found to have a 4-mm poorly differentiated cancer in her transverse colon on surveillance colonoscopy. The case is reported to advise practitioners of the need for meticulous colonoscopy in such patients.