Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.

PURPOSE: Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged > or = 65 years with long-term follow-up. PATIENTS AND METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. RESULTS: Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. CONCLUSION: When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.     

EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS

1. The rotation-mediated three-dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development. 2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose-dependent manner and interrupts normal monoaminergic development. 3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug-induced insults and a deficiency in monoamines persists throughout development. 4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype. 5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity.     

Tongue oximetry in children with extensive thermal injury: comparison with peripheral oximetry

We undertook a prospective study of standard peripheral pulse oximetry versus a modified pulse oximeter probe applied to the tongue in order to determine the efficacy of this alternative monitoring site in children with thermal injuries. Ten patients with a mean age (± SD) of 7.5 ± 4.5 yr were studied on 15 occasions. The mean weight +- SD) was 31.4+- 13.7 kg and percent surface area burn (± SD) was 56+- 21%. A total of 1,992 min of anaesthesia time was monitored. Both sites functioned simultaneously 47% of the time; the lingual but not the peripheral site functioned 28% of the time and only the peripheral site and not the lingual functioned 22% of the time. Neither site functioned 3% of the time. The tongue oximeter provided 563 min more monitoring time than the peripheral sites. The tongue oximeter also functioned in children with peripheral vasoconstriction when the peripheral sensor failed and was less susceptible to electrocautery interference. The tongue oximeter is a reasonable adjunct but not a substitute for peripheral oximetry since its application is limited to paralyzed, intubated patients.     

Biochemical markers surrogating on vascular effects of sex steroid hormones.

The main mechanism of possible cardioprotection by estrogens appears to be a direct effect on the vasculature, resulting in an improvement of endothelial function and inhibition of atherogenesis. Numerous observational and experimental studies have demonstrated a positive correlation between estrogens and various biochemical markers surrogating direct vascular effects. In general, most markers are influenced in a similar way by oral and transdermal hormone therapy, although oral therapy may have a faster and more pronounced effect. The main difference between oral and transdermal administration may be confined to markers that are mainly or exclusively produced in the liver. Clinical studies demonstrate that progestogen addition can have an impact on the beneficial estrogen-induced changes of biochemical markers. Concerning the effects of tibolone, inconsistent data have been found. Overall, tibolone-induced beneficial changes on the various biochemical markers appear to be less marked compared with those of hormone therapy. The few data available on the direct effects of androgens on the vascular wall indicate a less favorable action of androgens on biochemical markers than of estrogens. The practical relevance of marker measurements is currently under discussion. Although evidence strongly supports some of these markers as predictors of acute events, it remains to be established whether modifying circulating levels of these markers will influence outcomes.     

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

Rhenium-186 hydroxyethylidene diphosphonate (¹⁸⁶Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using ¹⁸⁶Re-HEDP Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the ¹⁸⁶Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq ¹⁸⁶Re-HEDP showed grade 3 toxicity (thrombocytes 25–50 × 10⁹/1), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% ± 10% IUA; range: 11%–44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of ¹⁸⁶Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of ¹⁸⁶Re-HEDP has been initiated.     

Early Teenage Substance Use as a Predictor of Educational-Vocational Failure

The authors report on the relationship of early adolescent substance use (up to the time of the 16th birthday) to educational-vocational performance in the early adulthood of 612 African-American urban subjects. Voluminous prospective data were available on the behavior, test performance, and families of 612 urban African-American subjects, from birth up to 7 years of age. Scarcer prospective data were available for school performance during later years of school. Control variables were derived from these data to determine the amount of variance in each dependent educational-vocational outcome variable that was accounted for, independently of the amount of variance accounted for by early substance use. (American Journal on Addictions 1994; 3:325–336)     

Liver resection without hilus preparation and with selective intrahepatic hilus stapling for benign tumors and liver metastasis

Background Nowadays, liver resection is a routine operative procedure in surgical centers, and strategies must be aimed at avoiding additional risk factors. Extrahepatic isolation of portal vein, hepatic artery and hepatic duct, as well as lymphadenectomy of the liver hilum are generally accepted steps of liver resection, even for metastatic and benign indications. Our primary aim was to analyze the feasibility, blood loss, blood transfusion requirements, incidence of complications, and outcome using the approach for intrahepatic devascularization leaving the extrahepatic hilus untouched. Materials and methods Thirty-eight consecutive patients with resection for metastases and benign liver tumors were selected. After hilar examination, the extrahepatic structures remain intact, and during parenchyma dissection, the whole right or left or the appropriate bi-segmental pedicle is isolated intrahepatically and then transected using a stapler device. Results The used technique was feasible in all cases, and no intra- or postoperative surgical complications were observed. To date, no tumor recurrence was found in the hilum during the follow-up period. Conclusion The intrahepatic pedicle stapling technique appears to be feasible and safe in liver resection. Hilar dissection can, thus, be avoided in liver metastasis and benign liver tumors.