Significance of screening in treatment and survival in bronchial carcinoma

In a retrospective study, the influence of the way bronchial carcinoma was detected was evaluated with respect to the possibility of surgery and to survival rates. From the 324 patients detected through mass screening (category I) 69.8% were suitable for surgery, whereas only 41.4% of the 736 patients detected because of pulmonary symptoms (category II) were deemed surgery-eligible. In category I, the type of surgical interventions were 65% (bi)lobectomy and 22.4% pneumonectomy. In category II, these figures were 23.4% and 53.6%, respectively. During the surgery, 10.6% turned out to be unresectable in category I, whereas 22.0% were in category II. There was also a marked difference in survival after 5 and 10 years. For category I, the 5-year survival rate was 23.4%, the 10-year survival 10.9%. In category II, these figures were 8.6% and 4.2%, respectively. The 5-year survival rate of all nonsurgically treated patients was 1% regardless of the method of diagnosis.     

A Post‐Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases

The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene‐specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger‐based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite‐stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost.     

Acute myocardial infarction and underlying stenosis severity.

OBJECTIVES: The objective of this study was to investigate the underlying stenosis severity of the culprit lesion in acute myocardial infarction. BACKGROUND: It is widely believed that myocardial infarction often occurs in angiographically mild luminal stenosis. This, however, is in contradiction with experience from interventional practice in primary PCI. METHODS: We performed quantitative coronary angiography (QCA) in 250 consecutive patients referred for acute percutaneous coronary intervention (PCI) because of acute myocardial infarction (AMI). Fundamental for analysis was that a realistic estimate of underlying luminal narrowing before the infarction could be made angiographically that QCA could be performed and that one of two criteria was met: (1) spontaneous reflow allowing assessment of the lumen proximal and distal to the culprit lesion, or (2) coronary artery closed at arrival but reflow after uncomplicated wiring allowing assessment of the lumen proximal and distal to the culprit lesion. RESULTS: Of 250 consecutive patients (mean age 61.7 +/- 12.7 years, 48 women) referred for acute PCI, 156 patients (62%) fulfilled at least one of the above criteria for reliable QCA. In 151 of these patients (96%) the severity of the underlying stenosis was >50% and in 103 (66%) it was >70%. There were no differences in stenosis severity between the left anterior descending [LAD, (72 +/- 13)%, n = 57], left circumflex [Cx, (74 +/- 10)%, n = 20], and right coronary artery territory [RCA, (74 +/- 12)%, n = 76] (ANOVA, P = 0.76). There were no differences in stenosis severity between women [(73 +/- 13)%, n = 36] and men [(75 +/- 11)%, n = 120; P = 0.35]. CONCLUSION: In contrast to what is often believed, the majority of myocardial infarctions occurs in significant stenosis.     

Variability in dentofacial phenotypes in four families with WNT10A mutations

This article describes the inter- and intra-familial phenotypic variability in four families with WNT10A mutations. Clinical characteristics of the patients range from mild to severe isolated tooth agenesis, over mild symptoms of ectodermal dysplasia, to more severe syndromic forms like odonto-onycho-dermal dysplasia (OODD) and Schöpf–Schulz–Passarge syndrome (SSPS). Recurrent WNT10A mutations were identified in all affected family members and the associated symptoms are presented with emphasis on the dentofacial phenotypes obtained with inter alia three-dimensional facial stereophotogrammetry. A comprehensive overview of the literature regarding WNT10A mutations, associated conditions and developmental defects is presented. We conclude that OODD and SSPS should be considered as variable expressions of the same WNT10A genotype. In all affected individuals, a dished-in facial appearance was observed which might be helpful in the clinical setting as a clue to the underlying genetic etiology.     

Early Assessment of Axillary Response with 18F-FDG PET/CT during Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: Implications for Surgical Management of the Axilla

Background

If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography–computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential ¹⁸F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II–III breast cancer.

Methods

A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUV_max) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.

Results

A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUV_max was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68–0.92) and 0.65 (95 % confidence interval 0.52–0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %—that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.

Conclusions

¹⁸F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Severity of single-vessel coronary arterial stenosis and duration of angina as determinants of recruitable collateral vessels during balloon angioplasty occlusion

To determine the factors that influence the presence of collateral vessels during coronary occlusion, we performed standardized contrast injection of the contralateral coronary artery in 58 consecutive patients, without previous myocardial infarction, undergoing percutaneous transluminal coronary angioplasty for 1-vessel disease (left anterior descending artery in 45, right coronary artery: in 10 and left circumflex artery in 3). The presence of collateral vessels during coronary occlusion, defined as partial or complete epicardial opacification by collateral vessels of the vessel dilated, was related to clinical, angiographic and electrocardiographic parameters. The angiographic appearance of collateral vessels during balloon inflation showed a weak, although statistically significant, correlation to the percent diameter stenosis before angioplasty (r = 0.28; p = 0.03) and the duration of angina (r = 0.37; p = 0.004). By combining lesion severity with the duration of angina, collateral vessels during coronary occlusion were particularly related to a lesion severity greater than or equal to 70% and duration of angina greater than or equal to 3 months (p less than 0.001). Furthermore, the presence of collateral vessels was associated with an absence of ST-segment shift (greater than or equal to 1 mm) during 1 minute of coronary occlusion (p less than 0.001).     

Automated classification of neonatal sleep states using EEG

Objective

To develop a method for automated neonatal sleep state classification based on EEG that can be applied over a wide range of age.