Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.     

Aminoglutethimide in postmenopausal breast cancer refractory to multiple hormonal and cytostatic treatments

Eighty-seven consecutive patients with metastatic breast cancer were treated with aminoglutethimide plus hydrocortisone. All patients were postmenopausal and had progressive disease following prior chemotherapy and endocrine therapy. Eighty-five women were evaluable for drug response. One patient showed complete remission and 14 patients partial response, for an overall response rate of 17%. The median duration of response was 11+ months. The response rate was highest in the presence of soft tissue involvement (36%). The most common side effects were transient skin rash, lethargy, and dizziness. Two patients discontinued treatment because of cutaneous allergy. Aminoglutethimide can be considered a moderately active agent when utilized as second- or third-line hormonal therapy.     

Serum Interferon (IFN)-Neutralizing Antibodies and Bioactivities of IFNs in Patients with Severe Type II Essential Mixed Cryoglobulinemia

The efficacy of alpha interferon (IFN-α) in the treatment of severe type II essential mixed cryoglobulinemia (EMC) has been reported previously. In some patients, the development of neutralizing antibodies to recombinant IFN-α (rIFN-α) can affect the clinical response achieved with rIFN-α; a second treatment with natural IFN-α preparations may reinduce the clinical response. In the present study the ability of leukocyte IFN (LeIFN) to restore the response was investigated from a pharmacodynamic viewpoint. Specifically, the pharmacodynamic profiles of different IFN-α preparations were studied by measuring the serum neopterin levels and the levels of expression of protein MxA mRNA in in vivo peripheral blood mononuclear cells in two patients with EMC whose resistance to rIFN-α2a treatment increased concomitantly with the development of neutralizing antibodies. These markers were measured before injection and at 24 and 48 h after a single injection of rIFN-α2a, consensus IFN [(C)IFN], or LeIFN. No increase or only a slight increase in MxA mRNA levels was detectable after administration of rIFN-α2a or (C)IFN, whereas a significant increase (≥10-fold) in MxA mRNA expression was recorded following administration of LeIFN. The neutralizing antibodies to rIFN-α2a cross-react with (C)IFN. Sera from these patients neutralized most but not all of the subtypes present in the natural IFN-α (LeIFN) mixture, and no significant increase in neopterin levels was observed after these patients were switched to LeIFN treatment. In summary, the data demonstrate that the problem of neutralizing antibodies still exists and that LeIFN may induce an increase in the level of MxA mRNA expression but not an increase in neopterin levels in patients who are resistant to treatment with rIFN-α2a or (C)IFN.     

Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate, and Fluorouracil in operable breast cancer.

PURPOSE: To assess the clinical relevance of different sequences of doxorubicin (DOX) and cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with operable breast cancer at risk of disease relapse. PATIENTS AND METHODS: Two randomized trials were activated in the early 1980s. The first study, in patients with one to three involved nodes, was intended to assess the effectiveness of intravenous (i.v.) CMF given every 3 weeks for 12 courses versus eight courses of the same CMF regimen followed by four courses of full-dose DOX (CMF-->DOX). The second study, in patients with more than three involved nodes, compared four courses of full-dose DOX sequentially followed by eight courses of i.v. CMF (DOX-->CMF) versus alternating two courses of the same CMF regimen with one course of DOX (CMF/DOX) for a total of 12 courses. RESULTS: After a median observation of 210 months, no statistically significant difference was documented in the first study (relapse-free survival hazard rate [HR], 1.06; total survival HR, 1.03). In contrast, the delivery of DOX first, followed by CMF significantly reduced the risk of disease relapse (HR, 0.68; 95% CI, 0.54 to 0.87; P =.0017) and death (HR, 0.74; 95% CI, 0.57 to 0.95; P =.018) compared with the alternating regimen. CONCLUSION: Anthracycline-containing regimens can further reduce the odds of relapse and death compared with CMF. However, the findings observed in our trials emphasize that the relative merits of anthracycline adjuvant programs also can depend on the modality of administration and must be assessed in properly designed trials in which the magnitude of the benefits can be weighed against potential risks.     

Bone Mineral Density is a Prognostic Factor for Postmenopausal Caucasian Women with Breast Cancer

Numerous studies have convincingly shown that women with low bone mineral density have lower risk of breast cancer. As many risk factors for breast cancer are also prognostic factors, we hypothesized that women with breast cancer and low bone mineral density will have lower breast cancer recurrence rates than women with normal bone densities. A prospectively collected data base of breast cancer patients was used to identify postmenopausal Caucasian women. Their records were reviewed and 309 patients with complete follow‐up and bone density tests within 1 year of their surgery were identified. The outcome of patients with low bone density (t > ?1.0) was compared to the outcome for patients with normal bone density (t < ?1.1). Among the 193 patients with invasive breast cancers and low bone density, distant disease‐free survival at 5 years was 96% compared to 84% for 114 patients with invasive breast cancers and normal bone density (p = 0.0239). Local disease‐free survival was 94% for low bone density patients compared to 86% for patients with normal bone densities (p = 0.0794). Bone mineral density is a significant prognostic factor for postmenopausal Caucasian women with breast cancer. Low bone mineral density is associated with a lower local and distant rate of recurrence.     

An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma

The incidence of pediatric adrenal cortical carcinoma (ACC) in southern Brazil is 10-15 times higher than that of pediatric ACC worldwide. Because childhood ACC is associated with Li-Fraumeni syndrome, we examined the cancer history and p53 status of 36 Brazilian patients and their families. Remarkably, 35 of 36 patients had an identical germ-line point mutation of p53 encoding an R337H amino acid substitution. Differences within intragenic polymorphic markers demonstrated that at least some mutant alleles arose independently, thus eliminating a founder effect. In tumor cells, the wild-type allele was deleted, and mutant p53 protein accumulated within the nuclei. Although these features are consistent with Li-Fraumeni syndrome-associated adrenal tumors, there was no history of increased cancer incidence among family members. Therefore, this inherited R337H p53 mutation represents a low-penetrance p53 allele that contributes in a tissue-specific manner to the development of pediatric ACC.     

Fecal Calprotectin Levels in Patients with Colonic Polyposis

Context The usefulness of stool calprotectin determination in diagnosis of inflammatory disease of the colon has been reported; information about its usefulness for patients with polyposis are scarce, however. Objective To evaluate the significance of stool calprotectin concentrations for patients affected by colonic polyposis. Patients Sixty-three consecutive patients (35 males, 28 females, mean age 60.3 years, range 39–78 years) were enrolled: 26 patients (41.3%) with polyps, 17 patients (27.0%) with asymptomatic diverticular disease, and 20 subjects (31.7%) with normal endoscopic appearance of the colon. Results Stool calprotectin concentrations were 17.4 ± 24.5 μg g⁻¹ for patients with colonic polyposis, significantly higher than concentrations for patients with diverticulosis (7.1 ± 5.7 μg g⁻¹; P = 0.026) or for patients with normal appearance of the colon (calprotectin 6.0 ± 5.8 μg g⁻¹; P = 0.003). For patients with a single polyp, stool calprotectin concentrations were similar to those for patients with multiple polyps. Calprotectin fecal concentrations for patients with sessile polyps and those with flat polyps were not significantly different. Calprotectin concentrations were not significantly related to the size of the polyps. Conclusion Our data show that colonic polyposis may cause an increase in stool calprotectin values and that these colonic lesions should be suspected when elevated stool calprotectin concentrations are found.     

Teachers as Learners: Developing Professionalism Feedback Skills via Observed Structured Teaching Encounters

This Conversations Starter article presents a selected research abstract from the 2017 Association of American Medical Colleges Southern Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of 4 experts who shared their thoughts stimulated by the study. These thoughts explore the value of the Observed Structured Teaching Encounter in providing structured opportunities for medical students to engage with the complexities of providing peer feedback on professionalism.     

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.