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BACKGROUND: Cooperative group trials and institutional series reported the risk of MDS and/or AML after adjuvant chemotherapy for early stage breast cancer (eg, NSABP 0.21%, Smith JCO 2003; ECOG 2197 0.5%, Goldstein ASCO 2012). We examined the incidence of MDS and/or AML in breast cancer survivors that are part of the NCCN Breast Cancer Outcomes Database. METHODS: The NCCN Database prospectively identifies all incident breast cancers diagnosed at participating cancer centers, and patients that continue their care at an NCCN site are followed annually with information collected on subsequent treatment, recurrence, and new cancers. Mortality is also ascertained for all diagnosed patients every 2 years through the National Death Index. Women with stages 1-3 breast cancer (BC) diagnosed between 1997- 2008 were included in this analysis. Univariate chi square analyses were used to compare characteristics between patients with BC and BC&MDS and/or AML. Time from BC to MDS and/or AML and 5-/10-year cumulative incidence rates were analyzed using proportional subdistribution hazards regression models that account for death as a competing risk to MDS and/or AML. RESULTS: Among 21563 stage 1-3 BC patients from 8 NCCN sites, 39 (0.18%) subsequently developed MDS and/or AML. Median overall follow-up was 4.7 years and median time from BC to MDS and/or AML was 2.8 years (range, 0.6 to 8.3 years). Cumulative MDS and/or AML incidence was 0.19% at 5y and 0.27% at 10y. Overall, cancer characteristics at BC diagnosis within BC&MDS and/or AML and within BC groups were similar (Caucasian 82%v82%, AA 8% v8%; ER+ 79%v75%, HER2+ 14%v21%, TNBC 15%v14%; contralateral BC 3%v2%; pancreas or ovarian cancer 0%v1%). 13191 had adjuvant chemo (75%v67%; anthracycline 89%v91%, AC-taxane 46%v35%, dose-dense 6%v5%). Trends observed included more patients in BC&MDS and/or AML group with prior radiation (85%v70%, p = 0.06) and older age at BC diagnosis (median age 59v54 years, p = 0.09). Risk for developing MDS and/or AML after BC (adjusted for age at BC and race) was increased in those receiving any chemotherapy versus no chemotherapy (HR 2.16, 95% CI 0.98-4.77, p = 0.06), any RT versus no RT (HR 2.44, 95% CI 1.01-5.88, p = 0.04), and if chemo/RT given versus just chemo or just RT (HR 2.2, 95% CI 1.05-4.59, p = 0.04). No increased risk was observed if a taxane was added to an anthracycline regimen (HR 1.27, 95% CI 0.57-2.81, p = 0.56). CONCLUSIONS: In a large national prospective registry across NCCN sites, risk of MDS and/or AML is increased after adjuvant chemotherapy and/or adjuvant radiation therapy for stages 1-3 breast cancer, especially if both are used. Specific population subsets will be further examined. These rates are similar to those observed in clinical trials, but may underestimate actual numbers due to patients lost to follow-up. In addition, an MDS diagnosis was routinely under-reported in population databases until recently. Strategies to limit risk of subsequent cancers in patients likely to survive early stage breast cancer should be considered at the time of initial diagnosis. Predictors of MDS and/or AML in breast cancer survivors are needed. [ABSTRACT FROM AUTHOR]

Review of the newborn nursery notes of 87 infants who had cystic fibrosis without meconium ileus (MI) indicated that 12 of them had clinical features consistent with the meconium plug syndrome (MPS). This high incidence of meconium abnormalities suggests that MI and the MPS probably represent different gradations of the same underlying pathologic abnormality. The findings further suggest that a quantitative pilocarpine iontophoresis sweat test be performed in every newborn infant with any type of meconium abnormality, including the spontaneous passage of meconium plugs.

The manifestations of cystic fibrosis (CF) may be minimal, absent, or overlooked during childhood, thus 8-10% of cases are diagnosed during adolescence. Between 1970 and 1982, 14/157 (8.9%) patients were diagnosed as having CF as teenagers, based on clinical findings and elevated sweat electrolyte levels. Of these 14 patients (means = 15 years, range = 12-20 years), 50% had pulmonary and gastrointestinal symptoms dating from childhood; 50% became symptomatic during adolescence (primarily with pulmonary manifestations). None had a family history of CF. Four had false-negative sweat tests resulting in a mean diagnostic delay of 7.3 years. Because of the potential long-term complications of CF on physical maturation, completion of the psychosocial tasks of adolescence, adaptation to a chronic illness, and issues of sexuality and fertility, consideration of this diagnosis is crucial.

A retrospective review was conducted of the charts of 271 patients with a diagnosis of cystic fibrosis (CF) who were evaluated over a 15-year period at the Johns Hopkins Hospital. Among these patients, eight were encountered in which the diagnosis of CF was made on the basis of a compatible clinical picture and at least two positive quantitative pilocarpine iontophoresis sweat tests but who were subsequently documented to have normal sweat electrolyte concentrations. Six of the eight patients had recurrent episodes of cough and wheezing without evidence of suppurative pulmonary disease. Our experience suggests that variability in sweat electrolyte concentrations may occur more commonly than is generally appreciated. In those patients who do not follow a typical course, it is crucial to repeat sweat tests, even if the initial diagnosis was based on two or more positive quantitative pilocarpine iontophoresis sweat tests performed in a CF referral center.

The sweat test is the only practical and reliable laboratory test for confirmation of the diagnosis of cystic fibrosis. Among 234 patients referred to The Johns Hopkins Hospital for sweat testing, 62 had had a previous test; 29 tests had been reported as negative, and 33 tests had been reported as positive. Results of quantitative pilocarpine-iontophoresis sweat tests at this center led to a change in diagnosis in 27 (43.5%) of these 62 patients. Most of the errors were false-positive.

A variety of intestinal complications, including constipation, abdominal pain, palpable cecal masses, intestinal obstruction, intussusception, and volvulus, have been observed beyond the neonatal period in patients with cystic fibrosis (CF). In a retrospective chart review of 63 patients with CF, we found evidence of one or more of these complications in 26 patients (41.3%). The incidence of intestinal complications was not related to overall disease severity, pulmonary exacerbations, history of meconium ileus at birth, or dose or type of pancreatic enzyme replacement. There was no change in the incidence of intestinal complications after patients switched to a pH-sensitive enteric-coated microsphere enzyme preparation.