Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853.

PURPOSE: In view of the increasing number of patients treated with breast-conserving treatment (BCT) for ductal carcinoma-in-situ (DCIS), risk factors for recurrence and metastasis should be identified. PATIENTS AND METHODS: Clinical and pathologic characteristics from patients with DCIS in the European Organization for Research and Treatment of Cancer trial 10853 (excision with or without radiotherapy) were related to the risk of recurrence. Pathologic features were derived from a central review of 863 of the 1,010 randomized cases (85%). The median follow-up was 5.4 years. RESULTS: Factors associated with an increased risk of local recurrence in the multivariate analysis were young age (< or = 40 years) (hazard ratio, 2.14; P =.02), symptomatic detection of DCIS (hazard ratio, 1.80; P =.008), growth pattern (solid and cribriform) (hazard ratios, 2.67 and 2.69, respectively; P =.012), involved margins (hazard ratio, 2.07; P =.0008), and treatment by local excision alone (hazard ratio, 1.74; P =.009). The risk of invasive recurrence was not related to the histologic type of DCIS (P =.63), but the risk of distant metastasis was significantly higher in poorly differentiated DCIS compared with well-differentiated DCIS (hazard ratio, 6.57; P =.01). CONCLUSION: Patients with poorly differentiated DCIS have a high risk of distant metastasis after invasive local recurrence. Margin status is the most important factor in the success of BCT for DCIS; additionally, young age and symptomatic detection of DCIS have negative prognostic value.     

Internal sclerostomy with the Er:YAG laser using a gradient-index (GRIN) endoscope

BACKGROUND AND OBJECTIVE: To show that sclerostomy, a glaucoma filtering surgery, can be performed using an Er:YAG laser. Scarring at the filtering site, a recurrent problem, may be reduced through proper positioning of the sclerostomy by using an intraocular endoscope. MATERIALS AND METHODS: Ab interno full-thickness sclerostomies were performed on eye bank eyes with an Er:YAG laser through a custom made optical delivery system. The intraocular laser probe consisted of a low OH silica fiber inserted in a metallic tapered sheathing. A rigid intraocular endoscope based on gradient-index lenses allowed visualization of the filtration site. RESULTS: A clear view of the anterior chamber angle was obtained through the endoscope, allowing for precise location of the sclerostomy. Full-thickness sclerostomies could then be performed at the desired location. Histologic sections showed thermal necrosis less than 50 microm thick in tissue adjacent to the sclerostomy. CONCLUSIONS: A sclerostomy performed with a combined procedure using an Er:YAG laser and intraocular endoscopy increases the speed of the procedure. The use of a high-resolution intraocular endoscope may increase the success rate of ab interno laser glaucoma surgeries.     

Pharmacokinetic interaction between high-dose methotrexate and oxacillin

An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate.     

Roles of the two active sites of somatic angiotensin-converting enzyme in the cleavage of angiotensin I and bradykinin: insights from selective inhibitors

Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each bearing a functional active site. The in vivo contribution of each active site to the release of angiotensin II (Ang II) and the inactivation of bradykinin (BK) is still unknown. To gain insights into the functional roles of these two active sites, the in vitro and in vivo effects of compounds able to selectively inhibit only one active site of ACE were determined, using radiolabeled Ang I or BK, as physiological substrates of ACE. In vitro studies indicated that a full inhibition of the Ang I and BK cleavage requires a blockade of the two ACE active sites. In contrast, in vivo experiments in mice demonstrated that the selective inhibition of either the N-domain or the C-domain of ACE by these inhibitors prevents the conversion of Ang I to Ang II, while BK protection requires the inhibition of the two ACE active sites. Thus, in vivo, the cleavage of Ang I and BK by ACE appears to obey to different mechanisms. Remarkably, in vivo the conversion of Ang I seems to involve the two active sites of ACE, free of inhibitor. Based on these findings, it might be suggested that the gene duplication of ACE in vertebrates may represent a means for regulating the cleavage of Ang I differently from that of BK.     

Assessment of irritant skin reactions using electrical impedance--a comparison between 2 laboratories

To assess interlaboratory variability in the measurement of skin electrical impedance (IMP), we evaluated irritant reactions to sodium lauryl sulfate (SLS) (2%) and nonanoic acid (NAA) (40%) in 2 laboratories. We studied the patch test responses in 40 healthy male and female volunteers between 20 and 30 years of age (20 in each laboratory) with an instrument for measuring IMP. 2 other bioengineering methods and visual scoring were also used to facilitate further illumination of any findings. A strict protocol including all details of the measurement procedure was carefully implemented in both laboratories. The skin reactions were evaluated at 23 h and at 3, 7 and 14 days after exposure. Our findings show that both irritants caused distinct dynamic responses detectable with the bioengineering techniques. Interestingly, the IMP baseline values varied between the 2 laboratories. Moreover, at early stages in the development of irritation (day 1), the irritants induced changes in IMP indices in the opposite direction, which accords with the concept of various IMP patterns of contact dermatitis caused by different irritants. Although the absolute values of IMP differed in both laboratories, the dynamic response patterns were the same.     

How long should patients with psychotic depression stay on the antipsychotic medication?

BACKGROUND: Patients who have major depression with psychotic features have greater morbidity and mortality than patients with nonpsychotic major depression. In particular, relapse and recurrence have been reported to occur more frequently in patients with psychotic depression than nonpsychotic depression. Despite the frequent relapse and recurrence in major depression with psychotic features, there are few studies of the efficacy of continuation and maintenance treatments. METHOD: Forty patients with a diagnosis of unipolar DSM-III-R major depression with psychotic features were treated with fluoxetine and perphenazine for 5 weeks after granting written informed consent. The patients who responded to treatment continued to receive the combination for an additional 3 months. If a patient was stable for 4 months on treatment with the combination, the patient was then gradually tapered off perphenazine treatment. For patients who exhibited impending relapse, perphenazine was restarted. Impending relapse was defined as any of the following: (1) symptoms meeting DSM-IV criteria for major depressive disorder (with or without psychotic features), (2) a total score of > or = 17 on the HAM-D, or (3) the presence of any psychotic symptoms. After 1 year of taking fluoxetine, patients were tapered off fluoxetine treatment. Data were gathered from 1992 to 1997. RESULTS: Thirty patients responded to the initial 5 weeks of treatment with perphenazine and fluoxetine. After taper of perphenazine following 4 months of treatment with fluoxetine and perphenazine, 22 (73%) of the 30 patients exhibited no signs of relapse over the next 11 months (8 months of fluoxetine monotherapy followed by a taper of fluoxetine and 3 additional months of assessment). Patients who showed signs of relapse after taper of the antipsychotic were more likely to have had a longer duration of the current episode and a history of more frequent past episodes and were more likely to be younger (under the age of 30 years). CONCLUSION: The data from this study suggest that a majority of patients who have major depression with psychotic features do not require treatment with antipsychotic medication for more than 4 months.