Nicotiana benthamiana plants expressing beet necrotic yellow vein virus (BNYVV) coat protein-specific scFv are partially protected against the establishment of the virus in the early stages of infection and its pathogenic effects in the late stages of infection

BACKGROUND: Screening for and the aggressive treatment of prostate carcinoma are controversial, but they are nevertheless being practiced in the U.S. Current clinical studies of the effectiveness of screening will take years to complete. Meanwhile, screening for prostate carcinoma is already having an effect on society. METHODS: National and regional trends in prostate carcinoma incidence and data on patient mortality and survival from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute are described in this article. SEER is a population-based cancer data base comprised of nine discrete areas. Fundamental principles of screening are used in this article to explain the impact that prostate carcinoma screening has had in the U.S. RESULTS: According to the data in the SEER registries, overall prostate carcinoma incidence rates increased at a far greater pace than prostate carcinoma mortality rates during the period 1973-1994. During that period, there was a shift in stage at diagnosis characterized by an increase in local and regional disease, and a decline in distant disease at diagnosis. Overall 5-year survival rates for prostate carcinoma patients also increased. The increase in incidence rates, the shift in stage at diagnosis, and the increase in survival rates are all evidence of increasing early detection. However, these changes are consistent with lead-time bias, length bias, a decline in mortality, and all three could have occurred. In the geographic SEER registries, the prostate carcinoma incidence rates vary markedly. These variations in incidence rates are due to regional variations in practice patterns and screening efforts. On the other hand, the SEER registries have comparable mortality rates. This is evidence of both lead-time bias and length bias. CONCLUSIONS: Substantial regional variations in incidence were found, but regional mortality rates were similar. This is evidence that screening and early detection efforts are resulting in the diagnosis of prostate carcinoma in some men who do not need therapy; thus, prostate carcinoma screening can lead to unnecessary treatment for such men. Furthermore, epidemiologic data do not demonstrate that screening is decreasing mortality. The benefits of screening and early detection, although theoretically possible, are yet unproven, whereas the risks and harms of screening and resultant treatment are definite.     

Race, treatment, and survival among colorectal carcinoma patients in an equal-access medical system

BACKGROUND: The aim of this study was to assess the influence of race on the treatment and survival of patients with colorectal carcinoma. METHODS: This retrospective cohort study included all white or black male veterans given a new diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers nationwide. After adjusting for patient demographics, comorbidity, distant metastases, and tumor location, the authors determined the likelihood of surgical resection, chemotherapy, radiation therapy, and death in each case. RESULTS: Of the 3176 veterans identified, 569 (17.9%) were black. Bivariate analyses and logistic regression revealed no significant differences in the proportions of patients undergoing surgical resection (70% vs. 73%, odds ratio 0.92, 95% confidence interval 0.74-1.15), chemotherapy (23% vs. 23%, odds ratio 0.99, 95% confidence interval 0.78-1.24), or radiation therapy (17% vs. 16%, odds ratio 1.10, 95% confidence interval 0.85-1.43) for black versus white patients. Five-year relative survival rates were similar for black and white patients (42% vs. 39%, respectively; P=0.16), though the adjusted mortality risk ratio was modestly increased (risk ratio 1.13, 95% confidence interval 1.01-1.28). CONCLUSIONS: Overall, race was not associated with the use of surgery, chemotherapy, or radiation therapy in the treatment of colorectal carcinoma among veterans seeking health care at Veterans Affairs Medical Centers. Although mortality from all causes was higher among black veterans with colorectal carcinoma, this finding may be attributed to underlying racial differences associated with survival. This study suggests that when there is equal access to care, there are no differences with regard to race.     

Colorectal cancer. Clinical and pathologic features

Despite an improved understanding of the pathogenesis of colorectal cancer and the technical ability to alter its natural history in a large proportion of average and high-risk patients, this cancer remains deadly. There has been no significant change in incidence or survival rates over the past 40 years. This indicates a continued need for earlier detection of polyps and cancers, aggressive surgery for the primary tumor, and improved multimodality treatment for metastatic disease.     

Protection by endoscopy against death from colorectal cancer. A case-control study among veterans

BACKGROUND: Although several clinical and epidemiologic studies suggest that timely diagnostic procedures of the large bowel may reduce mortality from colorectal cancer, the evidence for this relationship is primarily circumstantial. METHODS: A case-control study was conducted among hospitalized US military veterans to investigate whether diagnostic procedures of the large bowel were performed in the period preceding the diagnosis of colorectal cancer less frequently in patients dying of colorectal cancer than in control patients. Data files of a total of 4411 veterans dying of colorectal cancer between 1988 and 1992 were extracted from the records of the US Department of Veterans Affairs, Washington, DC. Data of four living control patients and four dead control patients without colorectal cancer were matched by age, sex, and race to each case patient. The case and the two control populations were compared by conditional logistic regression, calculating odds ratios, and their 95% confidence interval. RESULTS: Diagnostic procedures of the large bowel reduced mortality from colorectal cancer, the odds ratio being 0.41 (range, 0.33 to 0.50) for the comparison with living control patients. The protective effects of proctosigmoidoscopy, colonoscopy, and polypectomy lasted for 5 years. The procedures were protective against death from cancer of the colon, as well as cancer of the rectum. The most protective influence was associated with removal of tissue through biopsy, fulguration, and polypectomy. Similar influences were found comparing case patients with dead control patients. CONCLUSION: Removal of tissue represents the most effective means to reduce mortality from cancers of the large bowel. It retains its efficacy over a time period of 5 years.     

Colorectal cancer incidence and survival among Alaska Natives, 1969-1993

BACKGROUND: Although colorectal cancer rates are low among most groups of Native Americans in North America, rates for Alaska Natives have been substantially elevated compared with US rates for all races combined. METHODS: To better describe the epidemiology of colorectal cancer incidence and survival among Alaska Natives, stratified by gender and tribal/ethnic affiliation, we examined data collected by the Alaska Native Cancer Registry 1969-1993. We calculated age-adjusted and age-specific incidence as well as actuarial survival rates, and examined histological type, site, stage at diagnosis, and treatment. We compared these data to colorectal cancer data from whites living in western Washington. RESULTS: In all, 587 colorectal cancer cases were identified among Alaska Natives over the 25-year period, for an age-adjusted annual incidence rate of 71.4/100000 in women, and 69.3/100000 in men. Compared to Alaska Indians, colon cancer rates were significantly higher in Aleuts (relative risk [RR] = 1.6, 95% CI: 1.2-2.2) and in Eskimos (RR = 1.5, 95% CI: 1.2-1.8), while rectal cancer rates did not differ by race/ethnicity. Alaska Natives experienced a 50% higher incidence rate of colorectal cancer overall compared to western Washington whites (RR = 1.5, 95% CI: 1.3-1.6), although rectal cancer rates were similar in the two populations. The highest RR were seen among Alaska Native women; Aleuts and Eskimos had colon cancer rates more than twice that of western Washington white women. No unusual qualitative features were found in the cancers occurring in Alaska Natives. Actuarial colorectal cancer survival rates for Alaska Natives overall were 74% at one year and 42% at 5 years; these rates were very similar to those observed for the western Washington population. Both one and 5-year survival rates showed a significant trend towards improvement over time. CONCLUSIONS: Alaska Natives had substantially higher colorectal cancer incidence rates compared to western Washington whites. Rates were particularly high for Aleut and Eskimo women. These data suggest a need for intensified secondary prevention strategies for this high-risk population, while further research is needed to identify modifiable risk factors.     

Barium enema, proctosigmoidoscopy and upper gastrointestinal series in the preoperative evaluation of the cancer patient

Charts of 566 patients admitted to the Surgery Branch, National Cancer Institute over a five year period were reviewed. Routine upper gastrointestinal series was performed in 453 patients; barium enemas in 490; and proctosigmoidoscopies in 342. Upper gastrointestinal series detected no metastases or second primary malignancies but delineated the extent of large intra-abdominal tumors. Barium enema and proctosigmoidoscopy together revealed three unsuspected primary colonic tumors (1.2% in patients over 50 years of age). Sigmoidoscopy and examination of the stool for occult blood would have detected the same patients. Barium enema may be limited to surgical cancer patients in whom the extent of local tumor invasion is to be defined and to older patients in whom colonic tumors are suspected. Neither UGIS nor barium enema appear to be of value as a routine preoperative screening test in surgical cancer patients.     

Conditional survival estimates in 34,963 patients with invasive carcinoma of the colon

PURPOSE: We report colon cancer survival rates that are conditioned on patients having already survived one or more years after diagnosis. These rates have more meaning clinically, because they consider those patients who have already survived a given period of time after treatment. METHODS: The life table method was used to compute conditional survival rates, using population-based data obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Patients were diagnosed between 1983 and 1987 and followed up through 1994. Relative and observed survival rates are considered. RESULTS: Survival rates up to ten years after diagnosis are reported by stage of disease, gender, and race for colon cancer patients who survived from one to five years after diagnosis. Survival rates are also reported by lymph node involvement. CONCLUSIONS: Five-year and ten-year survival in colon cancer patients having already survived between one and five years after diagnosis continues to be influenced significantly by stage and race.     

Complex screening of family members at risk for familial adenomatous polyposis

151 members of 10 affected families with FAP have been registered at the authors' regional polyposis registry, among them 51 FAP patients were verified histologically. The disorder is autosomal dominant thus the chance for the inheritance of the mutated allele is fifty percent in the offspring of an affected patient. Because of the high risk the registration and regular control of family members is recommended. They can be divided into high risk and low risk group based on presymptomatic tests. The examination of retina pigmentepithel was the only possibility for presymptomatic diagnosis earlier. After localization and identification of APC gene responsible for the disease molecular genetic methods have been introduced for presymptomatic diagnosis. The authors performed presymptomatic tests based on ophthalmologic and molecular genetic methods among family members at risk. Ophthalmologic examination was done in 53 while molecular genetic investigation in 54 cases. All the results of endoscopic, ophthalmological and molecular genetic examinations were available in 35 persons, among them 19 FAP have been found. Ophthalmological examination were informative in 33 out 35 cases (unequivocal positive or negative) while results of molecular genetic methods and sigmoidoscopy were correlated in every case. Authors stress the significance of complex screening of affected families with FAP in the prevention of colorectal cancer and extracolonic malignant processes.     

Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

BACKGROUND: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. METHODS: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. RESULTS: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P < .05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.     

Primary malignant tumor of the breast. Monitoring after treatment

The appropriate follow-up of primary breast cancer patients is a controversial topic: an intensive surveillance is the rule for many oncologists, but the beneficial effect of this attitude has never been demonstrated. Two consensus conferences focused on this issue, both discouraged the routine use of laboratory tests, chest X-ray, radionuclide bone scan or liver echography which involve a high financial cost. For these routine investigations the sensitivity to detect recurrence is less than 5%. History and physical examination remain the best methods to detect a recurrence, and mammogram is helpful for detecting recurrent disease in the treated breast or a new primary cancer in the controlateral breast, which both are curable. The purpose of intensive follow-up is earlier detection of recurrence in order to treat as early as possible, but two randomized studies failed to demonstrate a survival benefit in 2600 patients. However with current treatments, only a follow-up study including a very large number of patients could detect a survival difference. The demonstration of an intensive follow-up benefit is similar in screening studies where it is recommended to use the most predictive, the less toxic and the less expensive test. Serum C.A. 15.3 level which best anticipates diagnosis in follow-up is one of the best candidates to be used in a randomized study.     

Estimation and projections of colorectal cancer trends in Italy

BACKGROUND: Occurrence of and prognosis for tumours of the colon and rectum are thought to be changing rapidly due to simultaneous changes in risk factor prevalence, early diagnosis and treatment. In this paper time trends of morbidity, survival and mortality for colorectal cancer during the period 1970-1990 are estimated and analysed. METHODS: Mortality trends were obtained from official death certificates. Relative survival rates were computed from population-based cancer registries. Incidence and prevalence rates were estimated from mortality and survival data. RESULTS: Incidence rates were increasing during the period considered, with a lower rate of increase for the youngest birth cohorts. Relative survival rates of both colon and rectum cancers were higher for women, and for younger age groups, and were positively associated with period of diagnosis. No significant survival difference among the cancer registries used was found. A total of about 155,000 prevalent cases, 40% of which had been diagnosed > or = 7 years before, were estimated in the Italian population for the year 1990. Mortality rates were slightly increasing for men and stable for women. Projections of colorectal cancer trends to the year 2000 indicate major expected rises in both incidence and prevalence. CONCLUSION: Colorectal cancer represents a problem of growing impact for health services in Italy. This conclusion can probably be extended to many developed countries.     

Multivariate analysis of the prognostic factors of patients with unresectable synchronous liver metastases from colorectal cancer

PURPOSE: It frequently is observed that widely varying prognoses are given for patients with the same extent of liver metastases from colorectal cancer, even though the same treatment is performed on these patients. One of the reasons for this variance is that prognostic factors for these patients have not been defined. This study was designed to elucidate which clinicopathologic factors were the most important in the prognosis of 73 patients with unresectable synchronous liver metastasis from colorectal cancer. METHODS: Univariate and multivariate analysis of 11 clinicopathologic factors were performed using the Cox proportional hazard model. Survival curves were generated using the Kaplan-Meier method. RESULTS: Extent of liver metastases was the most significant variable in this survival analysis, although the extent of lymph node metastases of the primary lesion also was significant. However, the method of treatment was not a significant determinant in the survival for patients with unresectable liver metastases. Median survival of patients with H1, H2, and H3 was 13, 12, and 6 months, respectively, and there was a significant difference between survival curves for patients with H1 and patients with H3. Median survival of patients with n0, n1, and n2 was 13, 7, and 7 months respectively, and there was a significant difference between survival curves for patients with n0 and patients with n2. Median survival of 6 patients with H1 and n0 and of 17 patients with H3 and n2 was 28 and 4 months, respectively. There was a significant difference in survival curves between these two groups. CONCLUSION: Longevity of patients with unresectable synchronous liver metastases from colorectal cancer is affected adversely by the presence of nodal metastases and extent of liver metastases. This should be considered in the planning treatment.     

Survival of patients with the most frequent malignant neoplasms in the population of Krakow in the years 1985-1989

In 1985-1989 there was not significant improvement of survival rates for the most common cancer sites in Cracow population. Survival of Cracow patients with colorectal, breast and larynx cancer and chronic lymphatic leukaemia were significantly below European mean. This situation is probably typical for whole Polish population.     

Reduction in risk of mortality from colorectal cancer by fecal occult blood screening with immunochemical hemagglutination test. A case-control study

Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case-control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17-0.92], 0.41 (95% CI 0.20-0.82), and 0.48 (95% CI 0.25-0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.     

Screening for colorectal cancer: a survey of New Zealand general practitioners

AIM: To determine the attitudes and reported behaviours of New Zealand general practitioners concerning colorectal cancer screening and diagnosis with special consideration of the use of faecal occult blood tests. METHOD: A postal survey of a random sample of 400 New Zealand general practitioners. RESULTS: The response rate to the survey was 63%. Most of the respondents did not support a screening programme for average risk patients but did support screening in high risk groups. General practitioners favoured a screening programme offered by themselves rather than a centrally organised screening programme. A majority of respondents agreed that there was a lack of clear guidelines and a need for education regarding screening for bowel cancer. CONCLUSION: Guidelines for colorectal cancer screening are required for New Zealand general practitioners. There appears to be a need for medical education concerning screening for colorectal cancer in particular and screening and prevention in general.     

Colorectal cancer in the young patient

Although predominantly a disease of older adults, colorectal cancer affects the younger population with an incidence of two to six per cent. It is thought to carry a less favorable prognosis in the young than in the general population. This may be due to advanced stage of the tumor at diagnosis. This study is composed of 37 patients, aged 40 and younger, treated over a 20-year period for colorectal cancer at Louisiana State University Medical Center-Shreveport and E. A. Conway Hospital. It was performed to investigate the incidence, stage at diagnosis, and prognosis of colorectal cancer in these young patients. The location of the primary tumor was fairly evenly distributed throughout the colon and rectum in this population. Pain, weight loss, rectal bleeding, and nausea and vomiting were the most common presenting symptoms. A family history of colon cancer or premalignant lesions were not risk factors in this study. Seventy per cent of all patients were treated with curative intent, and 42 per cent of these patients developed recurrent disease. The patients in this review presented with a higher incidence of advanced disease. Thirty-seven per cent of the lesions were Duke's C and 22 per cent were Duke's D, with poor 5-year survival (11% and 0%, respectively) when compared with national studies. The absolute 5-year survival for all young patients with colorectal cancer was 26 per cent (5 of 19 patients). It is important for the surgeon to be aware of the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.     

Improved survival of Hodgkin's patients in south-east Netherlands since 1972

In the past 30 years, staging and treatment of Hodgkin's disease have changed dramatically, and prolonged remission can now be induced in the majority of patients. Our purpose was to assess improvement in long-term survival, previously reported for specific patient groups, among unselected patients diagnosed and treated between 1972 and 1993 in general hospitals in South-East Netherlands. Data on all 345 Hodgkin's patients were derived from the population-based Eindhoven Cancer Registry; histopathology and clinical records were reviewed. Follow-up was attained up to 1994. Relative survival rates, i.e. the ratio of observed to expected rates, were 80% after 5, 70% after 10 and 67% after 15 years. Independent prognostic factors for lower overall survival were (in decreasing order of significance): advanced age, histology (lymphocyte depletion), advanced stage and earlier period of diagnosis. Distribution of age and stage did not change over the study period, but there was a modest increase in the incidence of the nodular sclerosis histological subtype. Crude 5-year survival rates improved from 60% in the period 1972-1976 to 81% in the period of 1987-1992 (P < 0.005). The largest improvement occurred in the 1970s and was most prominent among those aged over 50 years. As previously reported, cured Hodgkin's patients exhibit a higher mortality rate, which can be explained by treatment-related long-term complications such as second malignancies and cardiovascular diseases. The relatively high survival rates compared to other population-based studies may be attributable to the existence of a regional network within the framework of a comprehensive cancer centre. Better staging, new combinations of chemotherapy, improved radiation technology, advances in supportive care as well as more frequent intensive treatment of the elderly could explain the improvement in prognosis.     

The impact of patient's age on surgical therapy of colorectal liver metastases

In a consecutive series of 90 hepatic resections for colorectal liver metastases which were performed during a 10-year period at one institution, the influence of patient's age on surgical strategies and postoperative results was investigated. The mean age of all patients was 61 +/- 11 years with a range from 27-78 years; 19 patients (21%) were younger than 50 years and 18 patients (20%) were older than 70 years. Thirty-six (40%) major and 54 (60%) minor hepatic resections were performed. The postoperative complication rate was 26% and resection mortality 3%. Estimated overall median survival time was 27 months, operative mortality included. 1-, 3-, and 5-year survival rates were 78%, 45%, and 32%, respectively. Although there is some suggestion that selection criteria are more aggressive in younger patients, neither surgical procedures nor postoperative results were found to be determined by the numeric age of the patient in a significant way.     

Trends in survival from colonic cancer: the impact of subspecialization

BACKGROUND: Data from population-based registries have demonstrated a recent increase in case survival for colonic cancer which has been attributed to earlier diagnosis. The present study was performed to identify time trends in case survival for patients with colonic cancer in a single institution, and to identify factors associated with any such improvement. METHODS: Data regarding 1264 patients with colonic cancer who were diagnosed between January 1981 and December 1995 were obtained from the Royal Adelaide Hospital Cancer Registry. Prognostic factors examined were age, sex, Australian clinicopathologic stage (ACPS), differentiation and year of diagnosis. Survival analyses were performed using the Kaplan-Meier method, and differences between patient subgroups were tested using univariate and multivariate Cox analyses. Patterns of adjuvant therapy were stable throughout the study period. RESULTS: The study group comprised 1264 patients. Key independent predictors of case survival after controlling for covariables were found to be earlier-stage disease (P < 0.001), moderately or well differentiated tumours (P < 0.001), and more recently diagnosed tumours (P = 0.011). Specifically, the 5-year survival rates (+/- SE) increased from 40.3% (+/- 3.2) for 1981-83 to 48.3% (+/- 3.3) for 1984-86 and 51.6% (+/- 2.1) for 1987-95. This increase in case survival was temporally associated with the establishment of a specialty colorectal surgical unit within the Royal Adelaide Hospital. CONCLUSIONS: This study of patients with colonic cancer from a single institution confirms previously observed, population registry-based, increases in case survival over recent years. Such improvement was independent of trends in tumour stage and differentiation and the use of adjuvant therapies. This provides evidence that survival outcomes for colonic cancer are influenced by surgical expertise.     

Audit of colorectal cancer surgery by non-specialist surgeons

BACKGROUND: Some authorities recommend that colorectal cancer should be treated in specialist units but evidence that non-specialist units demonstrate comparatively poor results may be lacking. METHODS: Between 1987 and 1991, 267 patients were operated on by four general surgeons, none of whom was a specialist in colorectal surgery. Procedure-related complications, postoperative mortality and disease-related survival rates were analysed. RESULTS: There were four cases of intraperitoneal sepsis (1 per cent) and five of 189 patients (3 per cent) had clinical anastomotic dehiscence; there was no case of wound dehiscence. The postoperative mortality rate after elective and emergency surgery was 2 and 13 per cent respectively. The 5-year disease-related survival rate for curative and palliative surgery was 67 and 9 per cent respectively. There were no significant differences between the surgeons. CONCLUSION: Disease-related variables such as early-stage disease and fewer patients presenting as emergencies may have a greater favourable influence on ultimate survival than surgeon-related variables.