Patterns of care for non‐small cell lung cancer patients in Belgium: A population‐based study

Guidelines recommend surgery for Stage I‐II, chemoradiation for Stage III and systemic therapy for Stage IV non‐small cell lung cancer (NSCLC). However, patient related factors and patient preferences influence treatment decisions. We investigated patterns of care for Belgian NSCLC patients in 2010‐2011, based on population‐based data from the Belgian Cancer Registry and administrative databases. The relationship between patient characteristics, institutional diagnostic volume, type of treatment and survival was investigated. Overall, 20.8% of patients received no oncological treatment. 59% and 22.1% of Stage I‐II patients received primary surgery or (chemo)radiation respectively. 34% of Stage III patients received chemoradiation and 17% of Stage IIIA patients had surgery. 70% of Stage IV patients received chemotherapy or targeted therapy. Moderate variability between centres was observed. For Stage IV, systemic therapy was less frequently used in higher volume centres and 1‐year survival was lower in centres that had ≥ 50 new patients yearly. Although not all NSCLC patients received treatment as ideally recommended by guidelines, these results do not necessarily represent poor quality of care as patient characteristics and preferences need to be taken into account. Treatment options targeted towards patients with co‐morbidity or unfit patients is warranted to improve outcomes of all NSCLC patients.     

Lower serum zinc in major depression in relation to changes in serum acute phase proteins

There is now some evidence that major depression is accompanied by activation of the inflammatory response system (IRS). Other signs of IRS activation, which have been reported in major depression are lowered serum zinc (Zn) and serum albumin (Alb) concentrations. In serum, Zn is closely bound to Alb. The aims of the present study were to replicate previous findings that major depression is accompanied by lowered serum Zn and Alb and to examine whether the decrease in serum Zn may be explained by that in serum Alb. The above variables were determined in 48 major depressed patients and in 15 age-sex-matched healthy volunteers. Serum Zn and Alb were significantly lower in major depressed patients than in normal volunteers. In healthy volunteers and major depressed patients, there were significant and positive correlations between serum Zn and Alb. We found that 53.8% of the variance in serum Zn could be explained by the combined effects of serum Alb and diagnostic classification. The results suggest that lower serum Zn in depression is in part explained by lowered serum Alb and by another depression-related mechanism. It is suggested that lower serum Zn in depression may be secondary to sequestration of metallothionein in the liver, which may be related to increased production of interleukin-6.     

Plasmalyte: No Longer a Culprit in Causing False-Positive Galactomannan Test Results

False-positive galactomannan (GM) results have been reported in patients treated with gluconate-containing solutions, such as Plasmalyte. The GM optical density index was tested on 33 distinct batches of Plasmalyte and was found to be negative in all of the batches, confirming that Plasmalyte is no longer a cause of false-positive GM results.     

A gene for autosomal dominant hearing impairment (DFNA14) maps to a region on chromosome 4p16.3 that does not overlap the DFNA6 locus

Non-syndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 reported gene localisations. We have identified a large Dutch family with autosomal dominant non-syndromic sensorineural hearing impairment. In most patients, the onset of hearing impairment is in the first or second decade of life, with a slow decline in the following decades, which stops short of profound deafness. The hearing loss is bilateral, symmetrical, and only affects low and mid frequencies up to 2000 Hz. In view of the phenotypic similarities of this family with an American family that has been linked to chromosome 4p16.3 (DFNA6), we investigated linkage to the DFNA6 region. Lod score calculations confirmed linkage to this region with two point lod scores above 6. However, as haplotype analysis indicated that the genetic defect in this family is located in a 5.6 cM candidate region that does not overlap the DFNA6 region, the new locus has been named DFNA14.     

Chromosomal abnormalities in renal cell neoplasms associated with acquired renal cystic disease. A series studied by comparative genomic hybridization and fluorescence in situ hybridization

Sporadic renal cell carcinomas (RCCs) display different chromosomal abnormalities according to their morphology; gains of chromosomes 7 and 17 and loss of Y are commonly observed in papillary lesions, whereas loss of 3p sequences and multiple losses of specific chromosomes are found in non-papillary and chromophobe cell carcinomas, respectively. Acquired renal cystic disease (ARCD) is associated with an increased incidence of renal cell tumours, especially papillary lesions. The aim of this study was to examine a series of ARCD-related tumours for chromosomal abnormalities and to compare the findings with those abnormalities commonly observed in sporadic RCCs. Nine tumours from four patients with ARCD were examined using comparative genomic hybridization (CGH) and interphase cytogenetics. Gain of chromosomes 7 and 17 was observed in all four papillary lesions and loss of Y in three. In addition, gain of chromosome 16 was observed in three papillary tumours. Three chromophobe RCCs originating from the same kidney showed different genomic profiles; two had no abnormalities, whereas one showed loss of chromosome 17p. Two non-papillary RCCs failed to show chromosome 3p alterations. In conclusion, renal cell tumours developing in ARCD may show chromosomal abnormalities both similar to and different from those seen in sporadic tumours. Copyright © 1999 John Wiley & Sons, Ltd.     

Performance characteristics of specimen radiography for margin assessment for ductal carcinoma in situ: a systematic review

Background

Reducing positive margin rate (PMR) and reoperation rate in breast-conserving operations remains a challenge, mainly regarding ductal carcinoma in situ (DCIS). Intra-operative margin assessment tools have emerged to reduce PMR over the last decades, including specimen radiography (SR). No consensus has been reached on the reliability and efficacy of SR in DCIS.

Objective

We performed a systematic literature review to assess the performance characteristics of SR for margin assessment of breast lesions with pure DCIS and invasive cancers with DCIS components.

Methods

A literature search was conducted for diagnostic studies up to April 2017 concerning SR for intra-operative margin assessment of breast lesions with pure DCIS or with DCIS components. Studies reporting sensitivity and specificity calculated using final pathology report as reference test were included. Due to improved imaging technology, studies published more than 15 years ago were excluded. Methodological quality was assessed using quality assessment of diagnostic accuracy studies-2 checklist. Due to clinical and methodological diversity, meta-analysis was considered not useful.

Results

Of 235 citations identified, 9 met predefined inclusion criteria and documented diagnostic efficacy data. Sensitivity ranged from 22 to 77% and specificity ranged from 51 to 100%. Positive predictive value and negative predictive value ranged from 53 to 100% and 32 to 95%, respectively. High or unclear risk of bias was found in reference standard in 5 of 9 studies. High concerns regarding applicability of index test were found in 6 of 9 studies.

Conclusions

The present results do not support the routine use of intra-operative specimen radiography to reduce the rate of positive margins in patients undergoing breast-conserving surgery for pure DCIS or the DCIS component in invasive cancer. Future studies need to differentiate between initial and final specimen margin involvement. This could provide surgeons with a number needed to treat for a more applicable outcome.

     

Multiplex ligation-dependent probe amplification to detect subtelomeric rearrangements in routine diagnostics

Subtelomeric rearrangements are believed to be responsible for 5-7% of idiopathic mental retardation cases. Due to the relative complexity and high cost of the screening methods used till now, only preselected patient populations including mostly the more severely affected cases have been screened. Recently, multiplex ligation-dependent probe amplification (MLPA) has been adapted for use in subtelomeric screening, and we have incorporated this technique into routine diagnostics of our laboratory. Since the evaluation of MLPA as a screening method, we tested 275 unselected patients with idiopathic mental retardation and detected 12 possible subtelomeric aberrations: a der(11)t(11;20)(qter;qter), a 19pter duplication, a der(18)t(18;10)(qter; pter), a 15qter deletion, a 8pter deletion, a 6qter deletion, a der(X)t(X;1)(pter;qter), a der(X)t(X;3)(pter;pter), a 5qter duplication, a 3pter deletion, and two 3qter duplications. The patients can be subdivided into two groups: the first containing de novo rearrangements that are likely related to the clinical presentation of the patient and the second including aberrations also present in one of the parents that may or may not be causative of the mental retardation. In our patient cohort, five (1.8%) subtelomeric rearrangements were de novo, three (1.1%) rearrangements were familial and suggestively disease causing, and four (1.5%) were possible polymorphisms. This high frequency of subtelomeric abnormalities detected in an unselected population warrants further investigation about the feasibility of routine screening for subtelomeric aberrations in mentally retarded patients.