Showing papers on "Cancer published in 1988"

Genetic alterations during colorectal-tumor development.

Abstract: Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis.

Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.

Abstract: Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.

A cancer family syndrome in twenty-four kindreds.

Abstract: A search of the Cancer Family Registry of the National Cancer Institute revealed 24 kindreds with the syndrome of sarcoma, breast carcinoma, and other neoplasms in young patients. Cancer developed in an autosomal dominant pattern in 151 blood relatives, 119 (79%) of whom were affected before 45 years of age. These young patients had a total of 50 bone and soft tissue sarcomas of diverse histological subtypes and 28 breast cancers. Additional features of the syndrome included an excess of brain tumors (14 cases), leukemia (9 cases), and adrenocortical carcinoma (4 cases) before age 45 years. These neoplasms also accounted for 73% of the multiple primary cancers occurring in 15 family members. Six of these patients had second cancers linked to radiotherapy. The diversity of tumor types in this syndrome suggests pathogenetic mechanisms which differ from hereditary cancers arising in single organs or tissues. The syndrome is presently diagnosed on clinical grounds; laboratory markers are needed to identify high-risk individuals and families and to provide insights into susceptibility mechanisms that may be shared by a wide variety of cancers.

Photodynamic therapy of cancer.

Abstract: PDT represents another modality for the treatment of human malignancy. Photoactivated hematoporphyrins have definite antitumor activity in both in vitro and in vivo experimental systems. Much of the early clinical work involved treatment of patients with advanced, recurrent disease who had not responded to conventional therapy. Because good responses with acceptable toxicity have been obtained in these patients, active investigation continued and is aimed at defining the most appropriate sites and applications for the technique. Because of the limited depth of light penetration in tissue, the most promising sites may be those where there is limited thickness of tumor, such as in superficial skin lesions or carcinomas in situ involving the aerodigestive tract, bronchial tree, or genitourinary tract. Other potential uses include those where PDT could be combined with surgical or chemotherapeutic debulking, such as pleural mesothelioma or advanced stage ovarian cancer. Whether PDT can be of benefit in surgical cases where the margins of resection are close is an interesting but speculative notion at the present time. Clinical trials with hematoporphyrin derivative PDT in the sites mentioned are in progress. Laboratory work to better understand HpD also continues, as well as investigations into alternative photosensitizers with improved tumor localization, less cutaneous photosensitivity, and absorption peaks at deeper penetrating wavelengths of light. Attempts at measuring singlet oxygen, if successful, will permit the development of more meaningful dosimetry in order to correlate response with actual tissue levels of the purported cytotoxic agent. Hopefully, these and other developments in the field of PDT will improve the treatment for patients with cancer.

Estimates of the worldwide frequency of sixteen major cancers in 1980.

Abstract: The numbers of new cancer cases in 16 common sites occurring in 1980 have been estimated for 24 areas of the world for which the United Nations produces population estimates. For the world as a whole, the total number of new cases was 6.35 million, almost exactly evenly divided between the developed and developing countries. In males, the most important sites were lung, stomach, colon/rectum, mouth/pharynx, prostate and oesophagus, and in females breast, cervix, colon/rectum, stomach, corpus uteri and lung. When the two sexes are combined, stomach cancer emerges as the most common cancer in 1980 (669,400 new cases per year), but this estimate is only slightly greater than that of lung cancer (660,500 new cases), and comparisons with earlier estimates for 1975 suggest that, with declining incidence rates for stomach cancer and the continuing rise for lung cancer, the latter would become the most common cancer in the world by the end of 1981. The implications for cancer control in the developed and developing countries of the world are discussed.

The international incidence of childhood cancer

Abstract: The International Agency for Research on Cancer has coordinated a worldwide study of the incidence of cancer in childhood. Contributors from over 50 countries have provided data. This paper presents a summary of some of the major results. The incidence rates and relative frequencies of childhood cancers are described according to 12 diagnostic groups, defined mainly in terms of tumour morphology. Variations in the risk of those tumours between different countries and different ethnic groups provide important information on the relative importance of environmental and genetic factors in their aetiology.

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

Abstract: STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Case-control study of childhood cancer and exposure to 60-hz magnetic fields

Abstract: Concern with health effects of extremely low frequency magnetic fields has been raised by epidemiologic studies of childhood cancer in relation to proximity to electric power distribution lines. This case-control study was designed to assess the relation between residential exposure to magnetic fields and the development of childhood cancer. Eligible cases consisted of all 356 residents of the five-county 1970 Denver, Colorado Standard Metropolitan Statistical Area aged 0-14 years who were diagnosed with any form of cancer between 1976 and 1983. Controls were selected by random digit dialing to approximate the case distribution by age, sex, and telephone exchange area. Exposure was characterized through in-home electric and magnetic field measurements under low and high power use conditions and wire configuration codes, a surrogate measure of long-term magnetic field levels. Measured magnetic fields under low power use conditions had a modest association with cancer incidence; a cutoff score of 2.0 milligauss resulted in an odds ratio of 1.4 (95% confidence interval (CI) = 0.6-2.9) for total cancers and somewhat larger odds ratios (ORs) for leukemias (OR = 1.9), lymphomas (OR = 2.2), and soft tissue sarcomas (OR = 3.3). Neither magnetic fields (OR = 1.0) nor electric fields (OR = 0.9)more » under high power use conditions were related to total cancers. Wire codes associated with higher magnetic fields were more common among case than control homes. The odds ratio to contrast very high and high to very low, low, and buried wire codes was 1.5 (95% CI = 1.0-2.3) for total cases, with consistency across cancer subgroups except for brain cancer (OR = 2.0) and lymphomas (OR = 0.8). Contrasts of very high to buried wire code homes produced larger, less precise odds ratios of 2.3 for total cases, 2.9 for leukemias, and 3.3 for lymphomas.« less

Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study

Abstract: The associations between colorectal cancer risk and several chronic illnesses, operations and various medications were examined in 715 colorectal cancer cases and 727 age- and sex-matched controls in data derived from a large, comprehensive population-based study of this cancer conducted in Melbourne, Australia. There was a statistically significant deficit among cases of hypertension, heart disease, stroke, chronic chest disease and chronic arthritis and a statistically significant excess of ‘haemorrhoids’ among cases, and all of these differences were consistent for both colon and rectal cancers and for both males and females. Although no statistically significant differences were found for other cancers, there were twice as many breast cancers among cases (16) than among controls (8) and also there were 9 uterine cancers among cases and only 2 among controls. There was a statistically significant deficit among cases in the use of aspirin-containing medication and vitamin supplements and this was consistent for both colon and rectal cancers and for both males and females. There was a statistically significant excess of large bowel polypectomy among cases. The modelling of these significant associations simultaneously in a logistic regression equation indicated that hypertension, heart disease, chronic arthritis and aspirin use were each independent effects and consistent for both colon and rectal cancers for both males and females and also that these effects were independent of dietary risk factors previously described in the Melbourne study. The possible relevance of these findings towards an understanding of colorectal cancer risk and aetiology is discussed.

Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC).

Abstract: A randomized clinical trial was conducted by the European Organization for Research and Treatment for Cancer (EORTC) Gastrointestinal Cancer Cooperative Group to study the effectiveness of irradiation therapy administered in a dosage of 34.5 Gy, divided into 15 daily doses of 2.3 Gy each before radical surgery for rectal cancer (T2, T3, T4, NX, MO). Four hundred sixty-six patients were entered in the clinical trial between June 1976 and September 1981. Tolerance and side effects of preoperative irradiation were acceptable. The overall 5-year survival rates were similar in both groups. When considering only the 341 patients treated by surgery with a curative aim, the 5-year survival rates were 59.1% and 69.1% in the control group and in the combined modality group, respectively (p = 0.08). The local recurrence rates at 5 years were 30% and 15% in the control group and the adjuvant radiotherapy group, respectively (p = 0.003). Although this study did not show preoperative radiotherapy to have a statistically significant benefit on overall survival, it does have a clear effect on local control of rectal cancer. Therefore, before performing radical surgery, this adjuvant therapy should be administered to patients who have locally extended rectal cancer.

Localization of an ataxia-telangiectasia gene to chromosome 11q22–23

Abstract: Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood1,2 characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation3; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively4; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology5. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes6. Furthermore, heterozygous females are at an increased risk of breast cancer7,8. These findings, when coupled with an estimated carrier frequency of 0.5–5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene7 and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients10. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.

Body Iron Stores and the Risk of Cancer

Abstract: Because of evidence that increased body iron stores are associated with an increased risk of cancer, we examined iron status and cancer risk in the first National Health and Nutrition Examination Survey, a survey of more than 14,000 adults begun in 1971, with follow-up between 1981 and 1984. Among 242 men in whom cancer developed, the mean total iron-binding capacity was significantly lower (61.4 vs. 62.9 mumol per liter; P = 0.01) and transferrin saturation was significantly higher (33.1 vs. 30.7 percent; P = 0.002) than among 3113 men who remained free of cancer. The risk of cancer in men in each quartile of transferrin-saturation level relative to the lowest quartile was 1.00, 1.01, 1.10, and 1.37 (P = 0.02 for trend). The serum albumin level was significantly lower in men in whom cancer developed than in those who remained cancer-free. Among women, those in whom cancer developed did not have significantly lower total iron-binding capacity or higher transferrin saturation than those who remained cancer-free. However, a post hoc examination of 5367 women (203 with cancer) yielded a relative risk of 1.3 (95 percent confidence interval, 0.9 to 1.9) associated with a very high transferrin saturation (greater than or equal to 36.8 percent, a value in the highest quartile among men); in 5228 women with at least six years of follow-up (149 with cancer), the relative risk associated with transferrin saturation above this level was 1.5 (1.0 to 2.2). These results are consistent with the hypothesis that high body iron stores increase the risk of cancer in men. The possibility that a similar association exists in women requires further study.

Clonal Genomic Alterations in Glioma Malignancy Stages

Abstract: Comparison of constitutional and tumor genotypes at chromosomal loci defined by restriction fragment length alleles has proven useful in determining the genomic position and tissue specificity of recessive mutations that predispose to cancer (Hansen, M. F., and Cavenee, W. K. Cancer Res., 47: 5518–5527, 1987). Here we have applied this approach to 53 unrelated patients with glial tumors of varying histological malignancy grade. Loss of constitutional heterozygosity for loci on chromosome 10 was observed in 28 of 29 tumors histologically classified as glioblastoma (malignancy grade IV) whereas no similar losses were observed in any of 22 gliomas of lower malignancy grade. Examination of restriction fragment length alleles on other chromosomes revealed that loss of sequences on chromosomes 13, 17, or 22 had occurred at nonrandom frequencies and in at least one instance of each malignancy grade of adult glioma. The tumors in which loss of constitutional heterozygosity was observed were composed of one or a mixture of glial cell subtypes displaying astrocytic, oligodendrocytic, and/or ependymal differentiation. These results demonstrate a close association of the loss of chromosome 10 sequences with the most malignant histological stage of glioma and that glioblastoma arises as the clonal expansion of an earlier staged precursor. Furthermore they suggest that glioblastoma is a common phenotypic and malignancy terminus for glial tumors of various cellular subtypes which is reached through a common molecular pathway. This approach which involves the identification of malignancy stage specific somatic losses of heterozygosity provides a genotypic, rather than phenotypic, analysis of tumor progression.

Reduced Genomic 5-Methylcytosine Content in Human Colonic Neoplasia

Abstract: DNA methylation appears to play an important role in both physiological and experimentally modified gene expression, and alterations in DNA methylation have been described in animal tumor models and in transformed cells and tumor cell lines. However, there have been comparatively few reports on DNA methylation in primary human malignancies, and these reports are somewhat contradictory. While individual genes have shown hypomethylation in colon cancer and premalignant adenomas as well as in lung cancer, other genes have shown increased methylation, and absolute measures of 5-methylcytosine content have shown decreases in malignancies but not in premalignant adenomas. We have used a sensitive quantitative measurement of 5-methylcytosine content by high performance liquid chromatography revealing an unequivocal hypomethylation of tumor DNA. An average of 8 and 10% reduction in genomic 5-methylcytosine content was seen in apparently all colon adenomas and adenocarcinomas, respectively, and there was no significant difference between benign and malignant tumors. This is a substantial quantitative alteration and suggests a pervasive abnormality in the control of DNA methylation. Surprisingly, three patients with the highest 5-methylcytosine content in their normal colon appear to have a germline predisposition to cancer (Lynch syndrome).

The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice.

Abstract: When the human immunodeficiency virus transactivating gene under the control of the viral regulatory region is introduced into the germline of mice, skin lesions are induced that resemble Kaposi's sarcoma seen in AIDS. Our findings indicate that HIV could play a direct part in causing cancer.

Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families.

Abstract: Segregation analysis of breast cancer in families can provide the logical basis and the specific genetic models for mapping and identifying genes responsible for human breast cancer Patterns of breast cancer occurrence in families were investigated by complex segregation analysis In a sample of 1579 nuclear families ascertained through a population-based series of probands, an autosomal dominant model with a highly penetrant susceptibility allele fully explained disease clustering From the maximum-likelihood Mendelian model, the frequency of the susceptibility allele was 00006 in the general population, and lifetime risk of breast cancer was 082 among susceptible women and 008 among women without the susceptibility allele Inherited susceptibility affected only 4% of families in the sample: multiple cases of this relatively common disease occurred in other families by chance The same genetic models, with higher gene frequency, explained disease clustering in an extended kindred at high risk of breast cancer Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high-risk families can serve as models for understanding breast cancer in the population as a whole

Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres.

Abstract: A retrospective cohort of 823 patients with ulcerative colitis who resided at the time of diagnosis in one of three defined geographical areas (West Midlands region, Oxford region, England and Stockholm County, Sweden) was assembled. The patients were first seen at named hospitals in these areas and the diagnosis of ulcerative colitis established within five years of onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset of disease and were followed for a minimum of 17 years and a maximum of 38 years. Ninety seven per cent completeness of follow up was achieved. Examining the colorectal cancer risk in the series relative to the risk in the general population by standardised morbidity ratios, there was an eight fold increased risk of cancer in the series as a whole. Dividing the series by extent of colitis, extensive colitis patients showed a 19 fold increase in risk. A four fold increased risk was shown in the remainder of the series (left sided colitis, proctitis and extent unknown). Life table analyses in extensive colitis gave cumulative risks of 7.2% (CI 3.6-10.8) at 20 years from onset of disease and 16.5% (CI 9.0-24.0) at 30 years from onset. No significant effect of age at onset, sex or referral centre could be detected. Examination of the data by interval from onset to cancer and by actual age at development of cancer suggests that patients who develop colorectal cancer will do so in a distribution around 50 years of age independent of duration of disease in adult onset ulcerative colitis (greater than 15 years at onset of disease). An inverse relationship was shown between age at onset of disease and interval from onset of disease to cancer. Further age specific rates for cancer increased up to 50 years and decreased thereafter. These results suggest that extensive colitis patients have a genetic predisposition to colorectal cancer and that longstanding inflammation is not of primary importance in the initiation/promotion of cancer in this disease.

Expression of transforming growth factor α and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance

Abstract: We have studied the estrogenic regulation and the potential autocrine role of transforming growth factor alpha (TGF alpha) in the human breast cancer cell line MCF-7. A biologically active apparent mol wt 30 k TGF alpha was identified by gel filtration chromatography in medium conditioned by MCF-7 breast cancer cells. We previously reported induction of TGF alpha levels in medium by 17 beta-estradiol. We now report correlated increases in TGF alpha mRNA, by Northern and slot blot analysis, after estrogen treatment of MCF-7 cells in vitro. In vivo experiments confirmed these data: estrogen withdrawal from MCF-7 tumor-bearing nude mice resulted in a decline in tumor size and TGF alpha mRNA levels. To explore the functional significance of TGF alpha in MCF-7 cells, anti-TGF alpha antibody was added to MCF-7 soft agar cloning assays. Inhibition of MCF-7 growth resulted, supporting an autocrine role for TGF alpha. Further experiments using an anti-EGF receptor antibody expanded this data, demonstrating inhibition of estrogen-stimulated monolayer MCF-7 cell growth. Examining the generality of TGF alpha expression, 4.8 kilobase TGF alpha mRNAs were seen in three other human breast cancer cell lines, MDA-MB-231, ZR 75B, and T47D. Expression of TGF alpha mRNA was detected in 70% of estrogen receptor positive and negative primary human breast tumors from 40 patients when examined by slot blot and Northern analysis. Thus, we have demonstrated broad expression of TGF alpha in human breast cancer, its hormonal regulation in an estrogen-responsive cell line, and its possible functional significance in MCF-7 cell growth.

NIH conference. Hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma is the most frequent cancer worldwide, responsible for approximately 1,000,000 deaths annually, most of them in the Far East and in sub-Saharan Africa. It usually presents at an advanced stage and has a poor prognosis. There is evidence of an etiologic role for hepatitis B virus infection in the etiology of hepatocellular carcinoma. Carriers of the virus are 94 times more at risk for hepatocellular carcinoma than noncarriers. In many cases hepatitis B virus DNA is integrated within the cellular genome of the tumor. Programs have been established to detect hepatocellular carcinoma at an early stage; persons at high risk are regularly screened by measurement of serum alpha-fetoprotein levels and ultrasound examination of the liver. Surgical resection offers the only hope of cure at present, as chemotherapy, radiotherapy, and immunotherapy have not shown promise. Ideally, surgery should be done on small asymptomatic tumors.

Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers.

Abstract: We studied 670 persons in 34 kindreds by flexible proctosigmoidoscopic examination (60 cm) to determine how frequently colorectal adenomas and cancers result from an inherited susceptibility. Kindreds were selected through either a single person with an adenomatous polyp or a cluster of relatives with colonic cancer. The kindreds all had common colorectal cancers, not the rare inherited conditions familial polyposis coli and nonpolyposis inherited colorectal cancer. Likelihood analysis strongly supported the dominant inheritance of a susceptibility to colorectal adenomas and cancers, with a gene frequency of 19 percent. According to the most likely genetic model, adenomatous polyps and colorectal cancers occur only in genetically susceptible persons; however, the 95 percent confidence interval for this proportion was 53 to 100 percent. These results suggest that an inherited susceptibility to colonic adenomatous polyps and colorectal cancer is common and that it is responsible for the majority of colonic neoplasms observed clinically. The results also reinforce suggestions that first-degree relatives of patients with colorectal cancer should be screened for colonic tumors. This evidence of an inherited susceptibility to a cancer with well-recognized environmental risk factors supports the hypothesis that genetic and environmental factors interact in the formation and transformation of polyps.

The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer.

Abstract: Thromboembolic disease has long been recognized as a complication of cancer. Recent reports have suggested that drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may contribute to this risk, but it has not been possible to separate the effect of these drugs from that of the cancer. We performed a randomized trial comparing 12 weeks of chemohormonal therapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, doxorubicin, and tamoxifen) with 36 weeks of chemotherapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in patients with Stage II breast cancer. Among 205 patients randomly assigned to treatment, there were 14 episodes of thrombosis (6.8 percent). These 14 episodes occurred during 979 patient-months of chemotherapy; by comparison, there were no events during 2413 patient-months without therapy. During the first 12 weeks of the study, five patients in the 12-week group and four patients in the 36-week group had thrombosis. During the subsequent 24 weeks, when only patients in the 36-week group were still receiving chemotherapy, there was no thrombosis in the 12-week group, but there were five additional events in the 36-week group (P = 0.03). These findings suggest that chemotherapy contributes to thrombosis in patients with breast cancer.

Guidelines for clinical protocols for chronic lymphocytic leukemia: Recommendations of the national cancer institute-sponsored working group

Abstract: The National Cancer Institute (NCI)-sponsored Chronic Lymphocytic Leukemia (CLL) Working Group was convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials. We recognized the previous efforts in 1967 published again in 1973 as the report of the Chronic Leukemia-Myeloma Task Force [1] and 1978 of Cancer and Leukemia Group B (CALGB) [2]. We have used these reports for guidance during the current effort. Several noteworthy developments in the past few years have made it necessary to modify the previous guidelines. First, the diagnostic criteria for CLL and its clinical staging have been developed and well defined. Second, although staging systems facilitated entry of comparable and relatively homogeneous groups of patients in clinical trials, the definitions of response (CR) and partial response (PR) were not uniformly adopted from the previous guidelines in the clinical trials (Tables IA, IB); therefore, comparisons of results obtained in different studies became difficult. Third, there has been an improvement in our understanding of the immunology and biology of CLL. Finally, we are witnessing the emergence of several chemotherapy agents that promise impressive activity in CLL (e.g., 2′-deoxycoformycin [3], fludarabine monophos-phate [4,5]), and thereby offer the potential for improving survival time in this disease. To best identify regimens worthy of continued pursuit in large comparative trials, standardized guidelines for evaluation are essential. A number of laboratory investigations are also presented for which scientific interest is high yet relevance remains to be determined; thus, they are presented as companion studies to the clinical trials. This mechanism allows for flexibility in the testing of these questions and for additional ideas in the future without requiring modification of an entire treatment protocol.

Increasing incidence of primary brain lymphoma in the US.

Abstract: There have been a number of clinical reports suggesting an increasing incidence of primary brain lymphoma unrelated to acquired immune deficiency syndrome (AIDS) and organ transplantation. To investigate this issue, the US incidence of this rare lymphoma was assessed using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program (1973 through 1984). Never-married men, a relatively high risk group for AIDS, were excluded from the analyses. Brain lymphoma incidence increased from 2.7 in 1973 through 1975 to 7.5 cases per ten million population in 1982 through 1984 (chi-square trend, 15.25; P less than 0.001), and it increased among both men (chi-square trend, 6.74; P = 0.009) and women (chi-square trend, 10.48; P = 0.001). Increases in incidence also were observed among persons younger than 60 years of age (chi-square trend, 4.10; P = 0.04) and persons 60 years of age and older (chi-square trend, 9.16; P = 0.002). This increased incidence of brain lymphoma appears to be real: It antedates the AIDS epidemic and does not appear to be related to organ transplantation, another cause of increased risk of brain lymphoma. Although part of the increase may be an artifact of improvements in diagnostic technology and practice, most of the observed increase antedates the widespread use of such technologies. Finally, the increase in incidence of brain lymphoma does not appear to be related to overall trends in the incidence of brain tumors and non-Hodgkin's lymphoma, and it is not related to time trends in nosology.

Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC international case-control study in Turin and Varese (Italy), Zaragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France).

Abstract: A case-control study on larynx and hypopharynx cancer was carried out in 6 populations including the city of Turin and the province of Varese (Italy), the provinces of Navarra and Zaragoza (Spain), the canton of Geneva (Switzerland), and the departement of Calvados (France). This report presents an analysis of the risk associated with alcohol and tobacco consumption based on 1,147 male cases and 3,057 male population controls. Special attention was given to the study of the risk at various sites of larynx and hypopharynx. The effect of tobacco is similar for all sites and the risk associated with ever smoking is on the order of 10. The risks from alcohol drinking depend on site. They are similar for epilarynx and hypopharynx (RR = 4.3, for more than 80 g/day) and lower for endolarynx (RR = 2.1, for more than 80 g/day). For all sites the risk decreases after quitting (RR = 0.3 after 10 years); exclusive use of filter cigarettes is protective (RR = 0.5 relative to smokers of plain cigarettes only) as is exclusive use of blond tobacco (RR = 0.5 relative to smokers of black tobacco only). Inhalation increases the risk of endolaryngeal cancer but not that of hypopharynx or epilarynx. The relative risks for joint exposure to alcohol and tobacco are consistent with a multiplicative model.

Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide.

Abstract: THE syndrome of humoral hypercalcemia of cancer was first described by Fuller Albright in 1941.1 When a patient's hypercalcemia and hypophosphatemia resolved after the radiation of a single bone me...

The Medical Course of Cancer Patients With Fever and Neutropenia Clinical Identification of a Low-Risk Subgroup at Presentation

Abstract: • To determine whether cancer patients with fever and neutropenia differ in their medical stability, 261 medical records of 184 cancer patients who were hospitalized with fever and neutropenia and treated with conventional antibiotic therapy were studied to determine whether their presenting clinical characteristics influenced the likelihood of subsequent clinical events thought to require urgent medical attention. Overall, serious medical complications, including those without an obvious relationship to infection, occurred in 56 patient courses (21%). We distinguished three clinically determined subgroups of our study population at significantly higher risk than the remaining patient group, which seemed to be at low risk. Major complications occurred in 34 (34%) of 101 inpatients, 12 (55%) of 22 outpatients with concurrent comorbidity requiring inpatient care, and eight (31%) of 26 outpatients without concurrent comorbidity requiring inpatient care but with uncontrolled cancer. However, the remaining patients, who presented as outpatients without significant comorbidity or uncontrolled cancer, had major complications in only 2% of 112 hospitalizations. These results suggest that it may be possible to assess the medical stability of patients with fever and neutropenia based on presenting clinical features. If confirmed prospectively, these results may enable clinicians to identify groups of medically stable patients for whom conventional supportive care, including appropriately administered antibiotics, may be given safely under medical supervision of less intensity or of shorter duration than conventional treatment in the acute-care hospital setting. (Arch Intern Med1988;148:2561-2568)

Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables.

Abstract: From a cohort of 988 patients with differentiated thyroid carcinoma receiving primary surgical treatment between 1946 and 1970, we studied the 85 (9%) patients who had distant metastases diagnosed during life. Clinically detected metastases were found in 7% of the 859 patients with papillary cancers, 19% of the 100 patients with follicular cancers, and 34% of the 29 patients with Hurthle cell cancers. The total experience amounted to 607 patient-years of observation after the diagnosis of metastases, with a median follow-up in the 12 survivors of 23 yr (range, 13-32 yr). At the time of first diagnosis of metastases, the lungs only were involved in 53%, and bones only in 20%; 16% had multiple organ involvement. The overall mortality rates 5 and 10 yr after the diagnosis of metastases were 65% and 75%, respectively. Seventy-eight percent of all deaths were directly attributable to thyroid cancer; 82% of cancer deaths occurred within 5 yr. By univariate analysis, patient age, tumor extent, pattern of lung involvement, radioiodine uptake of the metastases, and radioiodine treatment were significant prognostic factors. By multivariate analysis, only age (as a continuous variable) at the time of first diagnosis of distant metastases (P less than 0.0001) and involvement of multiple organ sites (P = 0.0003) were independently associated with cancer mortality. The survival at 5 yr in 12 patients aged less than 40 yr with only a single organ involved was 92%. Older patients (aged greater than or equal to 40 yr) with a single metastasis (n = 59) had a lower survival (38% at 5 yr). The highest risk of cancer death (92% at 5 yr) was found in the 14 patients (any age) who at the time of first diagnosis of metastases had multiple organ involvement. The Cox regression model suggested that radioiodine therapy did not have a significant influence on survival, after adjusting for age and extent of metastatic involvement.