Ann Intern Med

Radiation therapy for breast cancer and increased risk for esophageal carcinoma.

Ahsan H. Neugut AI.
No information.
BACKGROUND: Several case reports have suggested an association between radiation therapy for breast cancer and the subsequent occurrence of esophageal carcinomas. OBJECTIVE: To examine the association between radiation therapy for breast cancer and subsequent esophageal squamous-cell carcinomas and adenocarcinomas. DESIGN: Population-based retrospective cohort study. SETTING: Population-based U.S. cancer registries. PATIENTS: 220,806 women in whom breast cancer was diagnosed between 1 January 1973 and 31 December 1993; 1,216,853 person-years of follow-up. MEASUREMENTS: Age- and period-adjusted standardized incidence ratio as a measure of relative risk for the second primary cancer. RESULTS: In women who had received radiation therapy for breast cancer, the relative risk for esophageal squamous-cell carcinoma increased to 5.42 (95% CI, 2.33 to 10.68) and the relative risk for esophageal adenocarcinoma increased to 4.22 (CI, 0.47 to 15.25) 10 or more years after radiation therapy. No increased risk was seen for either type of carcinoma among patients with breast cancer who did not receive radiation therapy. CONCLUSION: The risk for esophageal carcinoma is increased in women who receive radiation therapy for breast cancer.

Serious hepatitis A: an analysis of patients hospitalized during an urban epidemic in the United States.

Willner IR. Uhl MD. Howard SC. Williams EQ. Riely CA. Waters B.
University of Tennessee, Memphis 38163, USA.
BACKGROUND: Memphis and Shelby County, Tennessee, experienced an epidemic of hepatitis A in 1994 and 1995. More than 1700 cases were reported. OBJECTIVE: To characterize the clinical features of patients hospitalized during a large urban epidemic of hepatitis A. DESIGN: Retrospective chart review. SETTING: 15 acute care hospitals in Shelby County, Tennessee. PATIENTS: 256 patients hospitalized with acute hepatitis A. MEASUREMENTS: Laboratory findings (such as prothrombin time and bilirubin level), complications, and mortality. RESULTS: The median patient age was 26 years. Thirty-nine complications occurred in 35 patients. Twenty patients (8%) had extrahepatic complications, and 5 (2%) died. Patients 40 years of age and older were more likely to have serious complications, including death (P = 0.014). Sixty-seven patients (26%) presented with coagulopathy (prothrombin time > or = 3 seconds prolonged). Fifty-four patients (21%) had a bilirubin level greater than 170 micromol/L (10 mg/dL). CONCLUSIONS: During this epidemic, hepatitis A caused serious illness and death. Complications were more frequent in patients 40 years of age and older, but young, healthy persons were also at risk for severe complications.

Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis.

Aris RM. Renner JB. Winders AD. Buell HE. Riggs DB. Lester GE. Ontjes DA.
Division of Pulmonary Medicine, University of North Carolina at Chapel Hill 27599-7524, USA.
BACKGROUND: Osteoporosis occurs in patients with cystic fibrosis as they age, but its clinical implications are not well defined. OBJECTIVE: To determine the clinical effect of decreased bone mineral density in adults with cystic fibrosis and to assess possible clinical predictors of osteoporosis. DESIGN: Retrospective cohort study. SETTING: Academic cystic fibrosis center. PATIENTS: 70 adults with late-stage cystic fibrosis who were referred for lung transplantation. MEASUREMENTS: Bone mineral density was measured with dual-energy x-ray absorptiometry, patient-reported fracture events were confirmed by radiography, and kyphosis angles were measured by using the Cobb method. RESULTS: Mean bone mineral densities for the spine, femur, and total body were severely depressed in patients with cystic fibrosis, averaging 2 SDs below those of age-matched normal controls (P < 0.001). Patient interviews showed that 54 fractures had occurred over 1410 patient-years, and chest radiographs showed evidence of 14 additional rib and 62 additional vertebral compression fractures. The database (which covered 1410 patient-years) showed that fracture rates were approximately twofold greater in women with cystic fibrosis aged 16 to 34 years (P = 0.015) and men with cystic fibrosis aged 25 to 45 years (P = 0.04) than in the general population. Vertebral compression and rib fractures were 100- and 10-fold more common than expected, respectively (P < 0.001 for both comparisons). The mean kyphosis angle (+/- SD) for this group was markedly abnormal (44 +/- 14 degrees; 62% > or = 40 degrees) and probably contributed to diminished stature (mean height loss, 5.8 cm in men with cystic fibrosis and 5.9 cm in women with cystic fibrosis). Cumulative prednisone dose, body mass index, and age at puberty were the strongest predictors of bone mineral density. CONCLUSIONS: Osteoporosis is universal in adults with late-stage cystic fibrosis, and its complications include increased fracture rates and severe kyphosis.

The relation of physical activity to risk for symptomatic gallstone disease in men.

Year 1998
Leitzmann MF. Giovannucci EL. Rimm EB. Stampfer MJ. Spiegelman D. Wing AL. Willett WC.
Harvard School of Public Health, and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
BACKGROUND: Gallstone disease is a major source of morbidity in the United States. Gallstones are twice as common in women as in men, but severe biliary events leading to surgery occur with equal frequency in the two sexes. OBJECTIVE: To determine whether physical activity decreases risk for symptomatic gallstone disease in men. DESIGN: Prospective cohort study. SETTING: U.S. male health professionals. PATIENTS: 45,813 men 40 to 75 years of age were followed from 1986 to 1994. MEASUREMENTS: Questionnaires mailed in 1986, 1988, 1990, 1992, and 1994 asked about physical activity, incidence of gallstone disease, age, body weight, dietary and alcohol intake, smoking habits, use of medications, and occurrence of diagnosed medical conditions other than gallstone disease. RESULTS: 828 men reported having newly symptomatic gallstones (diagnosed by ultrasonography or radiography) or undergoing cholecystectomy for recent symptoms. After adjustment for multiple confounders, increased physical activity was inversely related to risk for symptomatic gallstone disease. When extreme quintiles were compared, men younger than 65 years of age had a stronger inverse association (multivariate relative risk, 0.58 [95% CI, 0.44 to 0.78]) with risk than did men 65 years of age or older (relative risk, 0.75 [CI, 0.52 to 1.09]). In contrast, sedentary behavior was positively related to risk for symptomatic gallstone disease. Men who watched television more than 40 hours per week had a higher risk for symptomatic gallstones than men who watched less than 6 hours per week (relative risk for older men, 3.32 [CI, 1.51 to 7.27]; relative risk for younger men, 1.58 [CI, 0.38 to 6.48]). CONCLUSIONS: Physical activity may play an important role in the prevention of symptomatic gallstone disease in men even beyond its benefit for control of body weight. The results of this study indicate that 34% of cases of symptomatic gallstone disease in men could be prevented by increasing exercise to 30 minutes of endurance-type training five times per week.

Postmenopausal hormone use and risk for colorectal cancer and adenoma.

Year 1998
Grodstein F. Martinez ME. Platz EA. Giovannucci E. Colditz GA. Kautzky M. Fuchs C. Stampfer MJ.
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
BACKGROUND: Accumulating evidence suggests that postmenopausal hormone use may decrease the risk for colorectal cancer. OBJECTIVE: To examine the relation of postmenopausal hormone therapy to colorectal adenoma and cancer. DESIGN: Prospective cohort and nested case-control studies. SETTING: Nurses' Health Study, a study of registered nurses recruited from 11 U.S. states. PARTICIPANTS: 59 002 postmenopausal participants in the Nurses' Health Study. MEASUREMENTS: Self-reported data on hormone use and cases of distal colorectal adenoma and colorectal cancer obtained from biennial questionnaires completed from 1980 to 1994. Cases of colorectal adenoma and cancer were confirmed by medical record review. RESULTS: 470 women developed colorectal cancer, and 838 developed distal colorectal adenomas. Current use of postmenopausal hormones was associated with a decreased risk for colorectal cancer (relative risk [RR], 0.65 [95% CI, 0.50 to 0.83]). This association was attenuated in past users (RR, 0.84 [CI, 0.67 to 1.05]) and disappeared 5 years after hormone use was discontinued (RR, 0.92 [CI, 0.70 to 1.21]). Longer duration of current use did not afford greater protection (RR with > or =5 years of use, 0.72 [CI, 0.53 to 0.96]). Even after exclusion of women who reported having screening sigmoidoscopy, the relative risk for colorectal cancer seen with current hormone use was 0.64 (CI, 0.49 to 0.82). This suggests that the apparent protection is unlikely to be due to more intensive screening among hormone users. Current users also had a lower risk for large (> or =1 cm) adenomas than did women who had never used hormones (RR, 0.74 [CI, 0.55 to 0.99]), although no overall material association was seen between colorectal adenoma and current hormone use (RR, 0.91 [CI,0.77 to 1.08]). CONCLUSIONS: The risk for colorectal cancer was decreased among women currently receiving postmenopausal hormone therapy, but the apparent reduction substantially diminished upon cessation of therapy. Hormone use was inversely associated with large colorectal adenomas but not small ones.

Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians Health Study.

Year 1998
Sturmer T. Glynn RJ. Lee IM. Manson JE. Buring JE. Hennekens CH.
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
BACKGROUND: In contrast to most observational studies, the randomized Physicians' Health Study found no association between aspirin use and colorectal cancer after 5 years. OBJECTIVE: To determine the effect of randomly assigned aspirin treatment and self-selected aspirin use on the incidence of colorectal cancer after 12 years and to identify factors influencing the self-selection of regular aspirin use. Design: Randomized clinical trial and prospective cohort study. SETTING: Male physicians throughout the United States. Patients: 22071 healthy male physicians who were 40 to 84 years of age in 1982. INTERVENTION: 325 mg of aspirin every other day. In 1988, the aspirin arm of the randomized trial was stopped early. Participants then chose to receive either aspirin or placebo for the rest of the study. MEASUREMENTS: Annual questionnaires asking about aspirin use and other variables, including occurrence of cancer. RESULTS: Colorectal cancer was diagnosed in 341 patients during the study period. Over 12 years of follow-up, random assignment to aspirin was associated with a relative risk for colorectal cancer of 1.03 (95% CI, 0.83 to 1.28). Various gastrointestinal symptoms and diagnoses were strong predictors of less frequent aspirin use in 1988. The relative risk for colorectal cancer in persons who used aspirin frequently after 1988 was 1.07 (CI, 0.75 to 1.53). CONCLUSIONS: In the Physicians' Health Study, both randomized and observational analyses indicate that there is no association between the use of aspirin and the incidence of colorectal cancer. The low dose of aspirin used and the short treatment period may account for the null findings. However, other characteristics associated with the use of aspirin in observational studies remain a plausible alternative explanation.

Incidence of hepatitis C in patients receiving different preparations of hepatitis B immunoglobulins after liver transplantation.

Year 1998
Feray C. Gigou M. Samuel D. Ducot B. Maisonneuve P. Reynes M. Bismuth A. Bismuth H.
Centre Hepato-Biliare, Laboratoire d'Anatomo-Pathologie et Transfusion Sanguine, Hopital Paul Brousse, and Universite Paris-Sud, Villejuif, France.
BACKGROUND: Recurrence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection after liver transplantation is a clinical problem. Polyclonal immunoglobulins against hepatitis B surface antigen (HBIGs) prevent the recurrence of HBV infection, but no effective prophylaxis is available for HCV infection. Before screening of blood donors was introduced in France, HBIGs may have contained antibody to HCV (anti-HCV). OBJECTIVE: To determine the influence of HBIG on the occurrence of hepatitis C after liver transplantation before and after 1990. DESIGN: Retrospective cohort study. SETTING: Liver transplantation unit of a university hospital. PATIENTS: 428 consecutive patients who had liver transplantation because of cirrhosis between 1984 and 1994. MEASUREMENTS: Detection of serum HCV RNA before and 1 year after transplantation and findings on liver graft biopsy. RESULTS: Among the 218 patients who had HCV infection before transplantation, the incidence of HCV viremia after transplantation was lower in those receiving HBIG than in those not receiving HBIG (25 of 46 patients [54%] compared with 162 of 172 patients [94%]; P < 0.001). In patients receiving HBIG, the incidence of HCV viremia after transplantation was lower among those who had transplantation before March 1990 than among those who had transplantation after this date (15 of 33 patients [45%] compared with 10 of 13 patients [77%]; P = 0.05). Among the 210 patients without HCV infection before transplantation, acquired infection was significantly less frequent in those receiving HBIG than in those not receiving HBIG (18 of 68 patients [26%] compared with 40 of 86 patients [47%]; P < 0.001). Passively transmitted anti-HCV was transiently detected in patients receiving HBIG before March 1990. Multivariate analysis in patients with HCV infection before transplantation showed that the absence of HBIG and transplantation after March 1990 were independent significant risk factors for chronic hepatitis C after transplantation. CONCLUSIONS: Polyclonal immunoglobulins that are treated for viral decontamination and contain anti-HCV could prevent HCV infection.

Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial.

Year 1998
Essell JH. Schroeder MT. Harman GS. Halvorson R. Lew V. Callander N. Snyder M. Lewis SK. Allerton JP. Thompson JM.
Wilford Hall Medical Center, Lackland Air Force Base, Texas, USA.
BACKGROUND: Hepatic complications are a major cause of illness and death after bone marrow transplantation. OBJECTIVE: To confirm the results of a pilot study that indicated that ursodiol prophylaxis could reduce the incidence of veno-occlusive disease of the liver. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Tertiary care teaching hospital. PATIENTS: 67 consecutive patients undergoing transplantation with allogeneic bone marrow (donated by a relative) in whom busulfan plus cyclophosphamide was used as the preparative regimen and cyclosporine plus methotrexate was used to prevent graft-versus-host disease. INTERVENTION: Before the preparative regimen was started, patients were randomly assigned to receive ursodiol, 300 mg twice daily (or 300 mg in the morning and 600 mg in the evening if body weight was > 90 kg), or placebo. MEASUREMENTS: Patients were prospectively evaluated for the clinical diagnosis of veno-occlusive disease, the occurrence of acute graft-versus-host disease, and survival. RESULTS: The incidence of veno-occlusive disease was 40% (13 of 32 patients) in placebo recipients and 15% (5 of 34 patients) in ursodiol recipients (P = 0.03). Assignment to placebo was the only pretransplantation characteristic that predicted the development of veno-occlusive disease. The most significant predictor of 100-day mortality was the diagnosis of veno-occlusive disease. The difference in actuarial risk for hematologic relapse in patients with chronic myelogenous leukemia and nonhepatic toxicities between the two groups was not statistically significant (13% in the ursodiol group and 20% in the placebo group; P > 0.2). CONCLUSION: Ursodiol prophylaxis seemed to decrease the incidence of hepatic complications after allogeneic bone marrow transplantation in patients who received a preparative regimen with busulfan plus cyclophosphamide.

Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost.

Year 1998
Climo MW. Israel DS. Wong ES. Williams D. Coudron P. Markowitz SM.
Hunter Holmes McGuire Veterans Affairs Medical Center, Medical College of Virginia, and Virginia Commonwealth University, Richmond 23249, USA.
BACKGROUND: Widespread antibiotic use has been associated with increases in both bacterial resistance and nosocomial infection. OBJECTIVE: To characterize the impact of hospital-wide clindamycin restriction on the incidence of Clostridium difficile-associated diarrhea and on antimicrobial prescribing practices. DESIGN: Prospective, observational cohort study. SETTING: University-affiliated Veterans Affairs Medical Center. PATIENTS: Hospitalized patients with symptomatic diarrhea. MEASUREMENTS: Clinical data on individual patients and data on antibiotic use were obtained from hospital pharmacy records. Hospital-wide use of antimicrobial agents was monitored. Isolates of C. difficile underwent antimicrobial susceptibility testing and molecular typing. RESULTS: An outbreak of C. difficile-associated diarrhea was caused by a clonal isolate of clindamycin-resistant C. difficile and was associated with increased use of clindamycin. Hospital-wide requirement of approval by an infectious disease consultant of clindamycin use led to an overall reduction in clindamycin use, a sustained reduction in the mean number of cases of C. difficile-associated diarrhea (11.5 cases/month compared with 3.33 cases/month; P < 0.001), and an increase in clindamycin susceptibility among C. difficile isolates (9% compared with 61%; P < 0.001). A parallel increase was noted in the use of and costs associated with other antibiotics with antianaerobic activity, including cefotetan, ticarcillin-clavulanate, and imipenem-cilastin. The hospital realized overall cost savings as a result of the decreased incidence of C. difficile-associated diarrhea. CONCLUSIONS: Hospital formulary restriction of clindamycin is an effective way to decrease the number of infections due to C. difficile. It can also lead to a return in clindamycin susceptibility among isolates and can effect cost savings to the hospital.

Increased risk for cancer in patients with the Peutz-Jeghers syndrome.

Year 1998
Boardman LA. Thibodeau SN. Schaid DJ. Lindor NM. McDonnell SK. Burgart LJ. Ahlquist DA. Podratz KC. Pittelkow M. Hartmann LC.
Mayo Clinic, Rochester, Minnesota 55905, USA.
BACKGROUND: Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up. RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.

Family history of colorectal adenomatous polyps and increased risk for colorectal cancer.

Year 1998
Ahsan H. Neugut AI. Garbowski GC. Jacobson JS. Forde KA. Treat MR. Waye JD.
The Herbert Irving Comprehensive Cancer Center and School of Public Health, Columbia University, New York, New York 10032, USA.
BACKGROUND: The risk for colorectal cancer among family members of patients with colorectal cancer is well established, but the risk among family members of patients with colorectal adenomas is less well established. OBJECTIVE: To examine the risk for colorectal cancer among first-degree relatives of patients with adenoma compared with that among first-degree relatives of controls without adenoma. DESIGN: Reconstructed cohort study. SETTING: Three university-based colonoscopy practices in New York City. PATIENTS: 1554 first-degree relatives of 244 patients with newly diagnosed adenomas and 2173 first-degree relatives of 362 endoscopically normal controls. MEASUREMENTS: Structured interviews were used to obtain family history. Adjusted relative risks (RR) were estimated from Cox proportional hazards regression models. RESULTS: The risk for colorectal cancer was elevated (RR, 1.74 [95% CI, 1.24 to 2.45]) among first-degree relatives of patients with newly diagnosed adenomas compared with the risk among first-degree relatives of controls. This increased risk was the same for parents (RR, 1.58 [CI, 1.07 to 2.34]) and siblings (RR, 1.58 [CI, 0.81 to 3.08]). First-degree relatives of patients with adenomas did not have elevated risk for other cancers. The risk for colorectal cancer among family members increased with decreasing age at diagnosis of adenoma in probands. Among first-degree relatives of patients who were 50 years of age or younger when the adenoma was diagnosed, the risk was more than four times greater (RR, 4.36 [CI, 2.24 to 8.51]) than that among first-degree relatives of patients who were older than 60 years of age when the adenoma was diagnosed. CONCLUSIONS: First-degree relatives of patients with newly diagnosed adenomas, particularly of patients who are 50 years of age or younger at diagnosis, are at increased risk for colorectal cancer and should undergo screening similar to that recommended for relatives of patients with colorectal cancer.