Bivalirudin for the treatment of patients with confirmed or suspected heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated response to unfractionated heparin and, less commonly, low molecular weight heparin. It is associated with a high thrombotic risk and the potential for limb and life-threatening complications. Argatroban is the only approved and currently available anticoagulant for HIT treatment in the USA. OBJECTIVES: To report safety and efficacy outcomes with bivalirudin for HIT treatment. METHODS: We retrospectively examined records from our registry of patients with a suspected, confirmed or previous history of HIT and who had received bivalirudin for anticoagulation in a single tertiary-care center over a 9-year period. RESULTS: We identified 461 patients who received bivalirudin: 220 (47.7%) were surgical patients, and 241 (52.3%) were medical patients. Of this population, 107 (23.2%) were critically ill, and 109 (23.6%) were dialysis-dependent. Suspected, confirmed and previous history of HIT were reported in 262, 124 and 75 patients, respectively. Of 386 patients with suspected or confirmed HIT, 223 patients (57.8%) had thrombosis at HIT diagnosis. New thrombosis was identified in 21 patients (4.6%) while they were on treatment with therapeutic doses of bivalirudin. No patient required HIT-related amputation. Major bleeding occurred in 35 patients (7.6%). We found a significant increase in major bleeding risk in the critically ill population (13.1%; odds ratio 2.4, 95% confidence interval 1.2-4.9, P = 0.014). The 30-day all-cause mortality rate was 14.5% (67 patients), and eight of 67 (1.7%) deaths were HIT-related. CONCLUSION: Bivalirudin may be an effective and safe alternative option for the treatment of both suspected and confirmed HIT, and appears to reduce the rate of HIT-related amputation.

Evaluation of changes in prostate specific antigen in clinically localized prostate cancer managed without initial therapy.

PURPOSE: We define changes in prostate specific antigen (PSA) measurements with time in 49 men 71.9 +/- 7.0 years old (mean plus or minus standard deviation) with clinically localized prostate cancer who remain untreated. MATERIALS AND METHODS: We retrospectively analyzed PSA changes in prostate cancer patients managed by watchful waiting. In all patients a minimum of 3 PSA levels were measured at intervals of at least 6 months after malignancy was diagnosed. The rate of change in serum PSA level with time (PSA velocity) was determined using an exponential, log linear model. RESULTS: In 49 patients treated conservatively mean initial PSA level plus or minus standard deviation was 12.3 +/- 11.1 ng./ml. and mean PSA followup during which no therapy for prostate cancer was introduced was 32.1 +/- 13.2 months. PSA levels decreased during the observation period in 11 of the 49 patients (22%) and median PSA doubling time in the remaining 38 was 55.7 months (range 15.1 to 994.5). There was no significant correlation between age at diagnosis, Gleason sum, initial PSA level or clinical stage and PSA velocity. The short-term rate of change in PSA during the first 9 months after prostate cancer was diagnosed correlated poorly with overall PSA velocity. The short-term rate of PSA change was greater than the overall rate of change in 14 of 37 patients (38%). CONCLUSIONS: There is significant variability in the rate of change of PSA with time in men with clinically localized prostate cancer who remain untreated. The usefulness of serial PSA measurements in the management of watchful waiting is unclear. Changes in PSA may not be helpful or appropriate in determining the need for therapy after a period of observation.

Trends in cancer mortality: perspectives from Italy and the United States.

Cancer continues to be a major public health problem in Italy, as it is throughout the world. We analyzed age-adjusted mortality rates for all cancers combined and for specific cancer sites in Italy for five year periods from 1950 to 1989. We compared trends in Italian cancer mortality to those observed in the United States during the same time period. We also considered some ancillary data including age-specific mortality rates, as well as incidence and five year relative survival data from the Modena Province. Age-adjusted cancer mortality rates in Italy are increasing in males and, to a lesser extent, females. This finding is in contrast to a recent plateau in age-adjusted cancer mortality rates in the United States. In Italy, stomach cancer mortality has declined substantially, counteracting marked increases in lung cancer mortality, particularly in males, and breast and lung cancer in females. Changes in cancer mortality in Italy, as in the US, have been driven primarily by changes in disease incidence rather than advances in therapeutics. These data suggest a need for realignment of cancer control resources toward prevention, particularly with regard to lung cancer and tobacco usage.

Cancer undefeated.

BACKGROUND: Despite decades of basic and clinical research and trials of promising new therapies, cancer remains a major cause of morbidity and mortality. We assessed overall progress against cancer in the United States from 1970 through 1994 by analyzing changes in age-adjusted mortality rates. METHODS: We obtained from the National Center for Health Statistics data on all deaths from cancer and from cancer at specific sites, as well as on deaths due to cancer according to age, race, and sex, for the years 1970 through 1994. We computed age-specific mortality rates and adjusted them to the age distribution of the U.S. population in 1990. RESULTS: Age-adjusted mortality due to cancer in 1994 (200.9 per 100,000 population) was 6.0 percent higher than the rate in 1970 (189.6 per 100,000). After decades of steady increases, the age-adjusted mortality due to all malignant neoplasms plateaued, then decreased by 1.0 percent from 1991 to 1994. The decline in mortality due to cancer was greatest among black males and among persons under 55 years of age. Mortality among white males 55 or older has also declined recently. These trends reflect a combination of changes in death rates from specific types of cancer, with important declines due to reduced cigarette smoking and improved screening and a mixture of increases and decreases in the incidence of types of cancer not closely related to tobacco use. CONCLUSIONS: The war against cancer is far from over. Observed changes in mortality due to cancer primarily reflect changing incidence or early detection. The effect of new treatments for cancer on mortality has been largely disappointing. The most promising approach to the control of cancer is a national commitment to prevention, with a concomitant rebalancing of the focus and funding of research.

Treatment of prostate cancer using external beam radiotherapy after laparoscopic pelvic lymph node dissection.

OBJECTIVES: To evaluate the results of prostatic irradiation in men with clinically localized prostate cancer and no laparoscopic evidence of nodal metastases compared with a cohort of patients who received radiation therapy with no prior surgical staging. PATIENTS AND METHODS: Thirty-one men with clinically localized prostate cancer and no evidence of pelvic nodal metastases after laparoscopic pelvic lymph node dissection received external beam radiation therapy to the prostate (65-70 Gy). The mean and median prostate specific antigen (PSA) levels in these men before treatment were 41.6 ng/mL and 28.0 ng/mL, respectively, and the mean Gleason sum was 6.1 (range 3-7). During the same interval, a group of 42 consecutive men with clinically localized prostate cancer were treated by external beam radiation therapy with no laparoscopic staging of the pelvic nodes. Treatment failure was defined by the development of bone metastases or a rising PSA level at least 6 months after the completion of radiotherapy. RESULTS: Radiation therapy was generally well tolerated after laparoscopy and no patient required hospitalization or surgery for side-effects related to the treatment. The median duration of follow-up in the 31 men who underwent laparoscopy was 21.5 months. The probability of treatment failure in this group was 41.8% and 56.3% with 24 and 30 months follow-up, respectively. When controlling for pre-treatment PSA level, grade and stage, there was no significant difference in the treatment failure rate between the groups treated with and without laparoscopic staging. CONCLUSIONS: These results suggest that there is no difference in treatment outcome with laparoscopic pelvic lymphadenectomy before external beam radiation therapy in high-risk patients who have significant pre-treatment elevations of PSA level.