Cyclophosphamide,methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high‐risk,premenopausal breast cancer

BACKGROUND:

The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single‐agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) against no adjuvant systemic therapy in high‐risk breast cancer patients. The authors report the results from that trial after a potential follow‐up of 25 years.

METHODS:

Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m² on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m² on Days 1 through 14 plus methotrexate 30 mg/m² and fluorouracil 500 mg/m² intravenously on Days 1 and 8 every 4 weeks for 12 cycles (the CMF arm).

RESULTS:

The 10‐year invasive disease‐free survival (IDFS) rate was 38.6% in the control arm compared with 55.5% in the C arm, 48.8% in the CMF arm, and 35.2% in the levamisole arm. Compared with the control arm, the hazard ratio for an IDFS event was 0.62 in the C arm (P = .001) and 0.70 in the CMF arm (P = .01). The hazard ratio for death was 0.70 in both the C arm (P = .02) and the CMF arm (P = .02) at 10 years, and the overall survival (OS) benefit was maintained during 25 years of follow‐up. No significant differences were observed in IDFS or OS between the C arm and the CMF arm or between the levamisole arm and the control arm.

CONCLUSIONS:

Compared with controls, both cyclophosphamide and CMF significantly improved disease‐free survival and OS, and the benefits persisted for at least 25 years in premenopausal patients who had high‐risk breast cancer. Cancer 2010. © 2010 American Cancer Society.     

Epithelioid cell cluster in cerebrospinal fluid: An unusual finding in tubercular meningitis

Tubercular meningitis is one of the serious manifestations of tuberculosis. It remains a significant contributor to the morbidity and mortality in children. Meningeal involvement in tuberculosis is detected by physical, chemical and cytological examination of cerebrospinal fluid (CSF). The cytological picture of CSF in tubercular meningitis is quite similar to that of viral meningitis showing a mixed population of lymphoid series cells. The presence of epithelioid cell cluster is very rare finding. We present here such a case of 2½ yr old boy who presented with fever off and on for 2 months and altered sensorium along with vomiting for 2–3 days. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Improved survival of patients with prostate cancer in northern Denmark, 1985-2004

OBJECTIVE: In 2003 prostate cancer was the commonest non-cutaneous cancer among men. In general, the prognosis for men with prostate cancer is less favourable in Denmark than in neighbouring countries. We aimed to examine possible changes in the long-term survival of patients with prostate cancer in four counties in Denmark during the period 1985-2004. MATERIAL AND METHODS: From four Danish counties (population 1.6 million) we included all patients (n=8928) with an incident discharge diagnosis of prostate cancer, as recorded in regional hospital discharge registries. We determined age-stratified survival and mortality rates, and used Cox proportional hazards regression to assess changes over time while controlling for age. RESULTS: The median age was 75 years (range 43-99 years). The number of patients increased during the four time periods, especially for those aged <70 years. The overall survival rate improved over time, in particular for the period 2001-04. One-year survival increased from 71% (1985-89) to 77% (2001-04). Overall 5-year survival was unchanged (26% and 28% for 1985-89 and 2001-04, respectively), whereas 5-year survival in patients aged <70 years improved from 35% in 1985-89 to 41% in 1995-99. Compared with the period 1985-89, the age-adjusted 1-year mortality rate ratio (MRR) was 0.79 (95% CI 0.70-0.89) (2000-04) and the age-adjusted 5-year MRR was 0.95 (95% CI 0.88-1.02 (1995-99). CONCLUSIONS: The survival of prostate cancer patients has improved in Denmark over the time period 1985-2005, and this change was most pronounced in men aged <70 years. These results may suggest a benefit from increasing use of prostate-specific antigen testing leading to an earlier diagnosis of prostate cancer, in some cases with a lower tumour burden.     

Conventional MRI is inadequate to delineate the relationship between the red nucleus and subthalamic nucleus in Parkinson's disease

BACKGROUND: An understanding of the relationships between the anterior commissure-posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus (RN) is imperative if these structures are to be used for targeting in deep brain stimulation. Currently, these relationships are incompletely understood and difficult to assess using conventional MRI. We examined the location and relationships of the STN and the RN to the AC-PC line and to each other in order to provide a greater understanding of their utility when targeting the STN, and the consistency of these anatomic relationships when examined using conventional MRI. METHODS: A total of 52 STN and RN in 26 patients with Parkinson's disease were evaluated on T2-weighted MR images. The anterior and posterior commissures and the border coordinates of the STN and RN were derived using frame coordinates. The distances from the midcommissural point (mcp) to the centers of the STN and RN, the diameters for each nucleus, and the distances between the nuclei were calculated in the x-, y-, and z-axes. RESULTS: The mean AC-PC length was 26.1 +/- 1.3 mm. The distance from the mcp to the center of the STN was 10 +/- 0.7 mm in the x-axis, 0.2 +/- 0.7 mm in the y-axis, and 3.3 +/- 0.9 mm in the z-axis. The distance from the mcp to the center of the RN was 4.7 +/- 0.6 mm in the x-axis, -5.9 +/- 1.0 mm in the y-axis, and 6.1 +/- 1.3 mm in the z-axis. The distance between the STN and RN was 2.3 +/- 0.7 mm in the x-axis, 2.1 +/- 1.0 mm in the y-axis, and -0.2 +/- 1.3 mm in the z-axis. CONCLUSIONS: Although recent studies imply that the RN can be used as a relatively consistent marker for the position of the STN, the present data suggest otherwise. These data indicate that a single targeting method may be inadequate given the resolution of conventional MRI, and that it is imperative to use multiple anatomical measurements when targeting the STN for deep brain stimulation in Parkinson's disease.     

Orthostatic side effects of clomipramine and moclobemide during treatment for depression

From a clinical point of view, orthostatic hypotension is a significant side effect during antidepressant treatment, particularly in the case of tricyclic antidepressants (TCAs). This prospective, randomized clinical trial evaluated the effects of clomipramine and moclobemide on orthostatic blood pressure during treatment for depression. One hundred and fifteen depressed inpatients, age up to 70 years, were randomized to treatment with either moclobemide (400 mg/day) or clomipramine (150 mg/day) after 1 week of placebo treatment. Orthostatic blood pressure was measured weekly over the 6-week study period. Clomipramine, but not moclobemide, caused a statistically significant fall in systolic (F = 9.37, P = 0.0037) and diastolic orthostatic blood pressure (F = 3.74, P = 0.0017). In the clomipramine-treated group of patients, we found no correlation between subjective complaints of orthostatic dizziness and the size of systolic orthostatic blood pressure. In conclusion, this study indicates that moclobemide does not induce orthostatic side effects, which is a significant problem in treatment with TCAs. However, the choice of antidepressants depends on other factors as well, e.g. the therapeutic efficacy.     

Cerebral gumma mimicking glioblastoma multiforme

This article reports an unusual case of a syphilitic gumma with a clinical and radiographical presentation initially suggestive of glioblastoma multiforme. Pathological evaluation was essential in establishing the diagnosis of neurosyphilis and in excluding neoplastic involvement. Cerebral gumma should be considered as part of the differential diagnosis of a midline intracranial lesion observed on magnetic resonance imaging.