Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort.

BACKGROUND: Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work). PATIENTS AND METHODS: The Women's Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status. RESULTS: Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58). CONCLUSIONS: In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking. CLINICALTRIALS.GOV: NCT00000611.

Understanding disparities in leukemia: a national study.

PURPOSE: Disparities in solid tumors have been well studied. However, disparities in hematologic malignancies have been relatively unexplored on population-based levels. The purpose of this study is to examine the relationship between race/ethnicity and acute leukemia mortality. METHODS: All patients with acute leukemia [acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML)] were identified in the Surveillance Epidemiology and End Results database, 1999-2008. Kaplan-Meier curves were generated to reflect survival probabilities by race/ethnicity. Multivariable Cox proportional hazard models estimated hazard of mortality by race with adjustment for individual (age, gender, year of diagnosis) and select genetic factors. RESULTS: A total of 39,002 patients with acute leukemia were included in the study. Overall, there was a mortality disparity in acute leukemia for blacks (HR 1.17, p < 0.0001) and Hispanics (HR 1.13, p < 0.0001) compared with non-Hispanic whites. In stratified analysis, disparities in ALL were greater than AML; blacks (HR[ALL]1.45, p < 0.0001; HR[AML]1.12, p < 0.0011); Hispanics (HR[ALL]1.46, p < 0.0001; HR[AML]1.06, p < 0.0001). Adjustment for individual patient and select genetic factors did not explain disparities. CONCLUSIONS: Blacks and Hispanics suffer decreased survival in acute leukemia as compared to others. Further investigation is needed to understand the drivers of poor cancer outcomes in these populations.

Issues faced by unaffected men with a family history of prostate cancer: a multidisciplinary overview.

PURPOSE: Despite the established importance of the role of family history in prostate cancer, relatively little research encompasses the psychosocial issues relevant to unaffected men with a family history of prostate cancer. To determine the completeness and quality of available literature on the issues faced by men with a high risk of prostate cancer, we conducted a multidisciplinary review of the literature to provide some guidance on the information that clinicians might provide to men who are concerned about family history. MATERIALS AND METHODS: A structured literature search was conducted by a multidisciplinary team of clinicians and researchers who reviewed the medical and psychosocial literature, and identified 21 relevant studies. RESULTS: Research suggests that many high risk patients are concerned about the risk of prostate cancer, and some may significantly overestimate that risk. Several studies have shown high screening rates among high risk patients and high levels of interest in genetic testing for prostate cancer risk should it become available, yet many men also report a desire for more information about their personal risk and risk management options. CONCLUSIONS: Given the lack of clear data on the efficacy of prostate cancer screening among high risk patients, clinicians could consider providing men who are concerned about family history with information on their personal risk, help them to clarify the potential benefits, limitations and harms of prostate cancer screening in their situation, and then support their choice regarding the management of prostate cancer risk.

The optimal form of urinary drainage after acute retention of urine.

OBJECTIVE: To assess the outcome of different forms of urinary drainage, particularly for urinary tract infection (UTI), operative findings and patient preference, in patients treated for acute urinary retention (AUR). PATIENTS AND METHODS: A feasibility trial was conducted of men presenting with AUR; after a short period of indwelling catheterization (IDC) patients were taught how to use clean intermittent self-catheterization (CISC). Patients who failed this were re-catheterized and taught to manage a valve, or failing this a leg bag, and then discharged home. The patients were followed to assess the occurrence of spontaneous voiding, UTI, findings at prostatectomy and patient satisfaction. RESULTS: The CISC group (34 men) had a higher rate of spontaneous voiding than the IDC group (16 men; 56% vs 25%). The incidence of UTI was 32% in the CISC and 75% in the IDC group. At TURP, 20% in the CISC group had a UTI, compared with 69% in the IDC group. Patients using CISC preferred it and had fewer complications than the IDC group. The CISC group had a similar ability to manage and similar acceptance of their method of drainage as the IDC group. CONCLUSION: CISC is managed and accepted well by patients who can use the technique and results in fewer UTIs. It should be considered in patients who present with AUR, and it may delay surgery.

Teaching normal physical examination in a large-group interactive using artists' models.

BACKGROUND: The innovative use of artists' models within the context of a large-group interactive teaching session, at Royal North Shore Hospital is reviewed. METHODS: The models were used to teach normal physical examination skills to a group of junior medical students, during their surgical rotation. This same group of students were also exposed to traditional bedside tutorials. The students evaluated both teaching experiences. RESULTS: In the four areas of evaluation (interaction, explanation, presentation, and organization), the large-group interactive sessions were consistently rated higher than the bedside tutorial (P < 0.001). CONCLUSIONS: The teaching technique is presented as an effective way of delivering quality clinical training to a group of junior medical students in an environment where access to good teaching material is becoming increasingly difficult.

Increased synthesis of matrix metalloproteinases by aortic smooth muscle cells is implicated in the etiopathogenesis of abdominal aortic aneurysms.

PURPOSE: The objective of this study was to identify the metalloproteinases elaborated by medial smooth muscle cells (SMCs) isolated from abdominal aortic aneurysm (AAA) and control arterial tissues and to ascertain if the levels produced by AAA SMCs were elevated. METHODS: SMC monolayers cultured from the outgrowth cells of tunica media explants were established, and their identity was determined by fluorescent microscopy by using a fluorescein isothiocyanate conjugated anti-SMC alpha-actin antibody. Matrix metalloproteinases (MMPs) produced by SMC monolayers in serum-free culture were examined by gelatin zymography and Western blotting with monoclonal antibodies to MMP-2, 3, and 9. RESULTS: Serum-free media from AAA SMCs contained metal-dependent elastolytic activity that cleaved the synthetic substrate succinyl trialanyl 4-nitroanilide (pH optima 7.2) and also 14C-insoluble elastin. The level of proteolytic activity found in these cultures was significantly greater than from control SMC media. Zymography established that AAA SMC media samples contained metal-dependent gelatinases of 50 to 64 and 92 kDa, which were identified respectively as MMP-2 and 9 by Western blotting by using monoclonal antibodies to these proteases. CONCLUSION: Medial SMCs isolated from AAA tissue produce significantly higher levels of MMP-9 and 2 than SMCs from control arterial tissues. These proteinases have the capacity to degrade elastin and a range of extracellular matrix proteins. From these data, we suggest SMCs may be involved in the abnormal degradation of the aortic wall in AAA through the excessive metalloproteinase activity produced by SMCs.

The incidence of deep venous thrombosis after laparoscopic cholecystectomy.

OBJECTIVE: To determine the incidence of deep venous thrombosis (DVT) after laparoscopic cholecystectomy. DESIGN: Prospective cross-sectional analysis, with a one-month follow-up, conducted in 1994. SETTING: University teaching hospital. SUBJECTS: 20 patients undergoing elective or urgent laparoscopic cholecystectomy, consecutively recruited. INTERVENTIONS: Patients received thromboprophylaxis according to the normal practice of the attending surgeon and underwent laparoscopic cholecystectomy. A venous duplex scan was performed before the operation and on Day 1, 7 and 30 after the operation. MAIN OUTCOME MEASURE: The presence of postoperative DVT. RESULTS: All patients were given graduated compression stockings to wear and 16 received electrical stimulation of the calf during the operation. Only 16 patients received pharmacological thromboprophylaxis before the operation, but all patients received this after the operation. The median duration of pneumoperitoneum was 80 minutes (40-160 minutes). Eleven of 19 patients completing all the required scans developed venous thrombosis (incidence, 55%); in three the thromboses involved major axial veins. In one patient the Day 7 and Day 30 scans were not performed, but the Day 1 scan was negative. Seven of the 11 thromboses were detected on the Day 1 scan. None of the DVTs were suspected clinically. CONCLUSIONS: This extremely high incidence of venous thrombosis correlates with the haemodynamic changes which occur in the venous system during pneumoperitoneum. Laparoscopic cholecystectomy should not be considered a procedure with a low risk of DVT, and further studies are needed to determine optimal DVT prophylaxis for laparoscopic surgery.

Smooth muscle cell migration and proliferation is enhanced in abdominal aortic aneurysms.

BACKGROUND: The aetiology of abdominal aortic aneurysms (AAA) is as yet undetermined. Smooth muscle cells (SMC) have been implicated in the pathogenesis of AAA as a result of their ability to produce elastin degrading proteases. The present study was undertaken to examine AAA SMC and aortic occlusive disease (AOD) SMC in terms of their respective migration and proliferation in vitro, in order to identify intrinsic differences between these cells. METHODS: Five AAA specimens, four AOD and five inferior mesenteric artery (IMA) specimens were established in culture. The cultures were examined for the extent and the rate of SMC outgrowth and proliferation. Cells were counted following trypsinization using a haemocytometer. RESULTS: For the AAA explants, the cellular outgrowths were first seen at 6.7 days, after culture initiation, while the corresponding outgrowth in the AOD group required 8.8 days (P < 0.05) and the IMA group 11.4 days (P < 0.05). AAA cells reached confluency at a mean of 22.4 days while AOD SMC required 28.6 days (P < 0.05) and IMA 31 days (P < 0.05). In the first passage, the time for AAA SMC doubling was 5.3 days compared to 6.2 days for AOD (P < 0.05) and 8.1 days for the IMA group (P < 0.05). Greater than 98% of the cells, in both groups, stained positive to SMC alpha-actin. CONCLUSION: From these data it is clear that there are intrinsic differences in cellular kinetics between SMC from the two disease states, supporting the hypothesis that AAA are not the result of atherosclerosis.

Ruptured abdominal aortic aneurysms: who should be offered surgery?

PURPOSE: Operation for ruptured abdominal aortic aneurysm is generally still associated with a high mortality rate. A review of our experience over a 9-year period was undertaken to identify factors present on admission associated with 30-day operative mortality. METHODS: A retrospective analysis of 154 patients with ruptured abdominal aortic aneurysm submitted for operation in a university teaching hospital between January 1985 and December 1993 was undertaken. RESULTS: The hospital mortality rate was 39%. Logistic regression identified a set of five independent preoperative factors associated with mortality: age (> 76 years), creatinine level (> 0.19 mmol/L), loss of consciousness after arrival, Hb (< 9 g%), and electrocardiographic ischemia. In the 52 patients with a single risk factor present, the mortality rate was 37%, with two factors (32 patients) it was 72%, with three or more factors (8 patients), it was 100%, and no patient had all five risk factors. A 16% mortality rate was found in the 62 patients with no risk factors. CONCLUSION: These risk factors can be easily determined on admission and may be used to help improve patient selection for surgical intervention. The current operative mortality rate for ruptured abdominal aortic aneurysm remains high, and in some cases health care resources are used in a nonproductive fashion. Restricted patient selection and allocation of scarce resources will bring advantages to both the patient and the community.

The economic cost of elective carotid endarterectomy.

Cost awareness and accountability for the use of health care resources have become major issues for clinicians. In order to identify the economic costs associated with carotid endarterectomy (CEA), a retrospective review of 50 elective CEA between May 1993 and April 1994 was undertaken. Despite our belief [based on the Australian National Diagnostic Related Groupings (ANDRG)], that our resource utilization had been refined to produce a median length of stay significantly below the New South Wales (NSW) State average, this study has identified several areas of non-productive expenditure. The mean cost of CEA per patient was $7053. This figure includes non-productive expenditure of $793 per patient in the pre-operative period and $395 per patient in the postoperative period. If these costs, which did not contribute to patient care, were removed the mean cost of CEA would be $5865. The major causes of non-productive resource utilization included prolonged pre-operative stay, duplicated or omitted investigations, as well as the use of the Intensive Care Unit for patient monitoring in the postoperative period.

Indications for laparoscopic pelvic lymph node dissection in the staging of prostate cancer.

Laparoscopic pelvic lymph node dissection is increasing in popularity, in the absence of validated surgical indications. This retrospective study was performed to identify those patients who would benefit from laparoscopic pelvic lymphadenectomy. The case notes of 50 patients who underwent bilateral open pelvic lymphadenectomy with frozen section examination were reviewed. The patients were staged clinically as having A2 (16), B1 (20) and B2 (14) prostate cancer. Except for the two patients who had macroscopically involved pelvic lymph nodes at operation, all proceeded to total prostatectomy. Six patients were found to have positive pelvic nodes. Of the six, four patients were clinical stage B2, one was B1 and one was A2. The Gleason score of two of these six patients was greater than seven. The prostate specific antigen (PSA) levels correlated more with high tumour volume (i.e. grade C) rather than with D1 disease. Frozen section at the time of lymphadenectomy had a false negative rate of 2 of 6. We conclude that laparoscopic pelvic lymph node dissections (LPLND) should be performed where there is a high likelihood of nodal disease, viz. bulky tumours, poorly differentiated histology and a high PSA reading. We consider that such selective use of LPLND optimizes its diagnostic utility while minimizing its unnecessary application.

Early congenital syphilis: clinico-radiologic features in 202 patients.

Venereal syphilis is highly prevalent among women of child-bearing age in Zambia. It is estimated to contribute 25-30% of the perinatal mortality rate of 50 per 1,000 births at the University Teaching Hospital in Lusaka. Because of multisystem involvement, early congenital syphilis, the offshoot of maternal syphilis, has varied criteria for its diagnosis. Therefore, in an attempt to draw guidelines for an easier and more reliable diagnosis, the authors analyzed the clinico-radiologic features of congenital syphilis in 202 patients. Although all infants were under the age of six months, there were several significant differences in the manifestations of the disease among neonates and the postneonates. The younger infants had a higher incidence of jaundice and mortality, whereas joint swellings, skin rash, snuffles, anemia, and periosteal reaction visible in x-rays of long bones were typical findings among the older group. The radiologic changes were seen in greater than 95% of patients in both groups. About 84% of mothers had attended prenatal clinics, but less than 20% of the women had been tested for syphilis. Since early congenital syphilis is common in many parts of the world and since all serologic tests have limitations, awareness of appropriate diagnostic criteria is recommended for all medical personnel.

Efficacy of gentamicin and kanamycin in the treatment of uncomplicated gonococcal urethritis in Zambia.

As a result of the sudden increase in the incidence of penicillinase-producing Neisseria gonorrhoeae (PPNG) from 3.2% in 1980 to 25% in 1982 at a sexually transmitted disease clinic in Lusaka, Zambia, an open clinical trial comparing single-dose gentamicin (280 mg) and kanamycin (2 g) was performed; the drugs were administered intramuscularly to male patients with gonococcal urethritis. Gentamicin was given to 302 men, 220 of whom were followed for two weeks. Kanamycin was given to 113 men, 89 of whom were followed for the same interval. Cure rates of 98% and 95%, respectively, were obtained. Both drugs were well tolerated, with no adverse reactions. All isolates were screened for penicillinase production by the rapid iodometric method; the incidence of PPNG was 41.0%. In view of the high incidence of PPNG associated with failures of penicillin treatment, this drug is no longer useful in situations like that studied here. Since gentamicin and kanamycin have proved to be effective, they are now recommended for the treatment of gonococcal urethritis in Zambia.

Penicillin and spectinomycin in treatment of gonococcal urethritis.

In view of the recent discovery of penicillinase-producing strains of Neisseria gonorrhoeae in Zambia, the efficacies of single intramuscular doses of aqueous procaine penicillin G (4.8 x 10(6) units plus 1 g of oral probenecid) and 2 g of spectinomycin were evaluated in an open clinical trial of the treatment of acute gonococcal urethritis in men. The former regimen was given to 123 men; failure of treatment was observed in 9.1% of the 88 men followed for two weeks. Spectinomycin was given to 124 men; treatment failure occurred in 3.8% of the 104 men followed for two weeks. During the trial, 190 unselected isolates of N. gonorrhoeae were screened by rapid iodometric test, and two penicillinase-producing strains were detected. MICs of penicillin and spectinomycin were determined by the agar dilution method for 110 and 98 isolates, respectively. MICs of penicillin of greater than or equal to 0.125 micrograms/ml were observed with 78.2% of the strains, while 83.7% had MICs of spectinomycin of less than or equal to 15.0 micrograms/ml. It was suggested that penicillin be given routinely for treatment of gonorrhea in Zambia and that spectinomycin be reserved for treatment of gonococcal infections not cured by penicillin.

Penicillinase-producing gonococcal strains in Zambia. Observations on treatment failures.

Penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) were detected in nine out of 27 (3.2%) treatment failures in 310 cases of acute gonococcal urethritis in men in Lusaka, Zambia. Minimum inhibitory concentrations of penicillin for 17.2% of 233 gonococcal isolates were less than or equal to 0.05 microgram/ml, for 38.2% between 0.125 and 0.25 microgram/ml, and for 46.6% greater than or equal to 0.5 microgram/ml. At present the prevalence of PPNG in African countries is not known but is likely to increase rapidly unless simplified control schemes are adopted within the existing health care programmes. Endemic pockets of PPNG in a few countries can threaten worldwide efforts to control gonorrhoea.