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Biomedical subjects

L B Travis

Publications and source records attributed to L B Travis.

At least 55 records · Page 3Linked to original sources
PubMed1995

Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma.

BACKGROUND: Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. PURPOSE: The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. METHODS: Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. RESULTS: A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. CONCLUSIONS: Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. IMPLICATIONS: The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders.

Aged↗
PubMed1995

Antiepileptic treatment and risk for hepatobiliary cancer and malignant lymphoma.

The possible influence of phenobarbital and phenytoin treatment on cancer risk was investigated in a case-control study nested in a cohort of 8004 epileptic patients in Denmark. Information on anticonvulsive treatments was abstracted for 95% of 60 patients with cancers of the liver and biliary tract or malignant lymphoma and for 94% of 171 cancer-free control patients. Use of anticonvulsive drugs was correlated with angiographic procedures that used Thorotrast, a well-known human liver carcinogen. After exclusion of study subjects exposed to Thorotrast, no association was seen between treatment with phenobarbital and cancer of the liver (odds ratio, 1.0; 95% confidence interval, 0.1-8.0) or biliary tract (odds ratio, 0.8; 95% confidence interval, 0.1-4.2). Furthermore, a histopathological evaluation of slides from 7 of 9 liver cancer patients not treated with Thorotrast revealed that 3 of the 4 cases of hepatocellular carcinoma involved cirrhosis of the liver, which suggested an etiological role for alcohol or viral hepatitis. A possible link was observed between use of phenytoin and risk for non-Hodgkin's lymphoma (1.8; 0.5-6.6), with a rising trend in risk with increasing dose. Our results suggest that the increased risk for cancers of the liver and biliary tract among Danish epileptic patients is likely to be due to Thorotrast administration and factors associated with cirrhosis of the liver rather than to anticonvulsive treatment.

Aged↗
PubMed1995

Lung cancer.

BACKGROUND: Lung cancer is the most common cause of cancer death in the United States, and its incidence has been rising for at least 50 years. Shifts in histologic type and differences in sex and race distribution have accompanied the increased incidence of lung malignancies. METHODS: Population-based data regarding lung cancer reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for the 15-year period 1973-1987 were analyzed. RESULTS: Results indicate that from 1973-1977 to 1983-1987, the age-adjusted rates of lung cancer increased by 30%, with the gain markedly greater in women (70%) than in men (17%). The largest percentage increases in age-adjusted rates were observed for small cell carcinoma and adenocarcinoma (approximately 60% each), with a more modest change for squamous cell carcinoma (+ 14%). For squamous cell carcinoma, the age-adjusted rates increased substantially for black (65%) and white (70%) women and only slightly for black men (10%), whereas it decreased slightly in recent years for white men. CONCLUSIONS: In recent years, adenocarcinoma has replaced squamous cell carcinoma as the most frequent histologic subtype for all sexes and races combined. These shifts in histologic types by sex and race may be related to differences in exposure to tobacco products, dietary factors, environmental or occupational carcinogens, and host characteristics. Increased use of transbronchial and needle biopsy may have also influenced these trends to some extent. Over the study period, 5-year relative survival rate did not change appreciably for lung cancer, suggesting that therapeutic advances have had little effect.

Adolescent↗
PubMed1995

Increased glomerular and urinary malondialdehyde in puromycin aminonucleoside-induced proteinuria in rats.

Puromycin aminonucleoside (PAN)-induced proteinuria in rats may be mediated by reactive oxygen metabolites (ROM), which are injurious to several cell components including membrane lipids. Increased malondialdehyde (MDA) production is indicative of lipid peroxidation. We examined if MDA content of glomeruli and its urinary excretion were increased in rats administered PAN. Of three groups of 8 Sprague-Dawley rats each, group 1 served a control, group 2 animals received a single intravenous injection of PAN (5 mg/100 g body weight) and group 3 animals PAN with intraperitoneal injections of dimethylthiourea (DMTU), a free radical scavenger of oxidants such as hydroxyl radicals, for 4 days. The rats were sacrificed on day 8 after PAN injection. Increasing proteinuria, starting on day 4, developed in animals in group 2 but not in the others. The glomerular MDA (nmol/mg protein) in group 2 animals was 2.93 +/- 1.91, significantly higher than 0.87 +/- 0.63 and 1.26 +/- 0.76 in groups 1 and 3, respectively. Urinary levels of MDA markedly increased in group 2 rats on day 3 and remained high thereafter, but no such increase occurred in the control animals and those administered PAN with DMTU; the latter was thus protective against PAN toxicity. Our observations support the view that ROM are involved in PAN-induced glomerular injury and that increased urinary MDA excretion can be a marker of ROM-mediated lipid peroxidation.

Animals↗
PubMed1994

Risk of leukemia following treatment for non-Hodgkin's lymphoma.

BACKGROUND: There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described. PURPOSE: Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL. METHODS: Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls. RESULTS: Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy. CONCLUSIONS: Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.

Aged↗
PubMed1994

Prompt remission of post-renal transplant nephrotic syndrome with high-dose cyclosporine.

A 2.8-year-old girl with focal segmental glomerulosclerosis had recurrence of nephrotic syndrome within 3 days of renal transplantation and the serum creatinine increased. Renal biopsy showed cellular rejection and also complete effacement of the epithelial cell foot processes. The rejection responded to methylprednisolone therapy but massive proteinuria persisted. An increase in the dose of cyclosporine A to 14 mg/kg per day was followed by immediate remission of the proteinuria. One month later, a second renal biopsy showed only focal fusion of foot processes. She remains free of proteinuria 2 years later. We propose that the higher dose of cyclosporine caused remission of the nephrotic syndrome.

Biopsy↗
PubMed1994

Hematopoietic malignancies and related disorders among benzene-exposed workers in China.

Although the relationship between benzene and acute nonlymphocytic leukemia (ANLL) is well established, most of the analytic cohort investigations examining the relationship between benzene and hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a follow-up study of 74,828 benzene-exposed and 35,805 non-exposed workers in China, pathology reports, medical records, and/or histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct classification and to provide clinicopathologic descriptions. Eighty-two patients with hematopoietic neoplasms and related disorders were identified among benzene-exposed workers, including 32 cases of acute leukemia, 7--myelodysplastic syndrome (MDS), 9--chronic granulocytic leukemia (CGL), 20--malignant lymphoma or related disorder (ML), 9--aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were observed, including 6 patients with acute leukemia, 2--CGL, 3--ML, and 2 others. The hematopathologic characteristics of the benzene-exposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatment-related ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to data, also indicate that a greater diversity of hematologic neoplasms is evident among benzene-exposed workers than previously described.

Adult↗
PubMed1993

Second cancers among long-term survivors of non-Hodgkin's lymphoma.

BACKGROUND: Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for second cancers. Few studies, however, include long-term survivors, and none report risk for second cancer among NHL patients surviving 15 or more years. PURPOSE: Our aim was to examine the pattern of second cancers among long-term survivors of NHL. METHODS: A cohort of 6171 patients diagnosed with NHL as a first primary cancer and who survived 2 or more years was identified within population-based tumor registries in Sweden, Ontario, and Iowa and within the affiliated tumor registry of The Netherlands Cancer Institute. Nearly 1000 NHL patients lived 15 or more years after diagnosis. Tumor registry files were searched for new invasive primary malignancies. RESULTS: Second cancers were reported in 541 subjects (observed-to-expected ratio [O/E] = 1.37; 95% confidence interval = 1.26-1.49), with significant excesses seen for all solid tumors (O/E = 1.28), acute nonlymphocytic leukemia (O/E = 4.83), melanoma (O/E = 2.38), Hodgkin's disease (O/E = 12.0), and cancers of the lung (O/E = 1.36), brain (O/E = 2.33), kidney (O/E = 2.07), and bladder (O/E = 1.77). Among 15-year survivors, significantly increased risks persisted for all second cancers (O/E = 1.45), solid tumors (O/E = 1.37), bladder cancer (O/E = 3.24), and Hodgkin's disease (O/E = 25.0). The actuarial risk of developing a second cancer 3-20 years after diagnosis of NHL was 21%, compared with a population expected cumulative risk of 15%. CONCLUSIONS: Patients with NHL continue to be at significantly elevated risk of second primary cancer for up to two decades following diagnosis. The pattern of risk suggests the influence of treatment as well as factors associated with the underlying disease. IMPLICATIONS: Quantitative studies of second cancer following NHL are needed to clarify the role of antecedent therapy, shared risk factors, host susceptibility, and other etiologic and diagnostic influences. Despite the generally advanced age of patients with NHL, the persistently elevated risk of second cancers should alert clinicians to the importance of continued medical surveillance.

Adolescent↗
PubMed1992

Second cancers in patients with chronic lymphocytic leukemia.

BACKGROUND: Reports to date have provided widely divergent estimates of the risk of second malignant neoplasms in patients with chronic lymphocytic leukemia (CLL), ranging from cancer deficits to excesses of twofold to threefold. PURPOSE: Our purpose was to estimate the risk of second primary cancers following CLL, utilizing population-based tumor registries, and to determine whether site-specific excesses might be associated with type of initial treatment for CLL. METHODS: We analyzed data for 9456 patients diagnosed with CLL as a first primary cancer between 1973 and 1988, who were reported to one of nine tumor registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and who survived 2 or more months. SEER files were searched for invasive primary malignancies that developed at least 2 months after the initial CLL diagnosis. RESULTS: Compared with the general population, CLL patients demonstrated a significantly increased risk of developing all second cancers (840 observed; observed-to-expected ratio [O/E] = 1.28; 95% confidence interval [CI] = 1.19-1.37). Significant excesses were noted for cancers of the lung (O/E = 1.90), brain (O/E = 1.98), and eye (intraocular melanoma) (O/E = 3.97) as well as malignant melanoma (O/E = 2.79) and Hodgkin's disease (O/E = 7.69). Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis. CONCLUSION: CLL patients are at a significantly increased risk of developing a second malignant neoplasm. The pattern of cancer excesses suggests a susceptibility state permitting the development of selected second malignancies in patients with CLL, perhaps because of shared etiologic factors, immunologic impairment, and/or other influences. Although our results do not suggest a strong treatment effect, more detailed studies of second tumors in CLL are needed to investigate the role of radiation therapy and chemotherapy.

Aged↗
PubMed1992

Hodgkin's disease following non-Hodgkin's lymphoma.

The risk of Hodgkin's disease following non-Hodgkin's lymphoma (NHL) was estimated using information collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Histopathologic material representing both diagnoses was reviewed for 11 patients in whom Hodgkin's disease was reported after NHL. Diagnoses of both diseases were confirmed in nine patients. Comparisons with population rates indicated that patients with NHL are at an almost threefold risk of subsequently having Hodgkin's disease. Survival in this series was poor; seven of the nine patients died within 16 months after the diagnosis of Hodgkin's disease.

Adult↗
PubMed1992

Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus.

To test the hypothesis that bone mineral density (BMD) is lower in children with insulin-dependent diabetes mellitus (IDDM), we measured BMD of the lumbar vertebrae (L-2 to L-4) by dual-photon absorptiometry in 31 boys and 25 girls, mean age 12.3 years, with IDDM of varying clinical duration (range 0.1 to 14.8 years). Mean standard deviation scores (z scores) were determined for L-2-L-4 BMD, weight, height, weight percentile, and weight-adjusted L-2-L-4 BMD index (L-2-L-4 BMD/weight), with reference data from a previously described white, nondiabetic, age-matched control group (n = 221). Compared with nondiabetic control subjects, male patients with short-term IDDM and all female patients with IDDM did not have significantly different L-2-L-4 BMD, weight, weight percentile, height, or BMD index. Boys with IDDM longer than 1 year had significantly lower weight, weight percentile, and height than did age-matched control subjects. When L-2-L-4 BMD of boys with long-term diabetes was corrected for weight, the L-2-L-4 BMD index was significantly greater than that of control subjects, indicating that weight was disproportionately lower than BMD. There were no significant linear correlations between metabolic control and L-2-L-4 BMD. When L-2-L-4 BMD was adjusted for differences in body weight, spinal BMD values in children with IDDM were not lower than in control subjects. These findings indicate that in children with IDDM, as in previously studied nondiabetic youths, body weight and spinal BMD are highly correlated; although BMD is reduced in some children with diabetes, the reduction parallels reductions in growth, and may simply reflect a normal response of the skeleton to a lower weight-bearing load.

Absorptiometry, Photon↗
PubMed1992

Comprehensive evaluation of a Thorotrast patient: an overview.

For several decades, thousands of people received Thorotrast during the course of angiography and other radiologic procedures. Eventually, as the hazards of this radioactive, radiographic contrast agent became apparent, research was initiated to further evaluate its associated adverse effects. In 1988 and 1989, Charles W. Mays, together with colleagues at a variety of sites, developed a detailed protocol for the comprehensive postmortem evaluation of one subject who had been administered Thorotrast 36 y previously. This case represents the first holistic approach to the analysis of Thorotrast in a whole body, simultaneously assembling clinical and autopsy findings with dosimetric, radiochemical, autoradiographic, and molecular evaluations.

Aged↗