Sentinel node biopsy in breast cancer : aspects on validation, diagnostics and lymphatic drainage pattern

Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. Determination of axillary status is crucial in clinical decision-making. Total axillary lymphadenectomy is generally accepted as a reliable staging procedure. Routine axillary lymph node dissection (ALND) is being increasingly replaced by sentinel node biopsy (SNB) - detection and analysis of the first lymph node that drains the tumour. Immediate, complete ALND after SNB has confirmed that tumour-negative sentinel nodes accurately predict tumour-free axillary nodes in clinically node-negative breast cancer patients. This thesis validates the feasibility and accuracy of SNB in palpable and non-palpable breast cancer, and in women who have had an open biopsy procedure prior to SNB. It also discusses the short-term outcome of patients undergoing SNB as the only axillary procedure and showing a tumour-free sentinel node. Sentinel node biopsy was performed in stages T1 and T2 and clinically node-negative breast cancer patients. A confirmative axillary dissection was performed in paper I and the first part of paper III, whereas in the application phase of paper III, lymph node dissection was performed only in those patients who had metastases in the sentinel lymph node. The detection rate of SN was 90% in palpable tumours in the learning study (n=498 women; paper I), 95% in 57 women with non-palpable tumours and 96% in 75 women with an earlier breast biopsy (paper III). The false-negative rate was 11% in the learning study (paper I), 5.5% in the group of nonpalpable tumours, and 10% among those with an earlier open biopsy (paper III). In the application phase (paper III), 745 patients with non-palpable breast cancer and 86 patients with prior intervention were included. The detection rates were 95.3% (710/745) and 90.7% (78/86), respectively. During the follow-up time of almost 2 years, no axillary relapse was found among the 103 patients with a positive SLN that was followed by ALND. Two axillary relapses were found among the 607 patients with a negative SNB. No axillary relapse was found among women who had had an open biopsy procedure prior to SNB (paper III). All sentinel nodes were submitted for histopathological processing using frozen-section examination with hematoxylin-eosin staining (H&E). In a separate study, H&E was compared with immunohistochemistry with cytokeratin antibodies (MC), and imprint cytology (IC) (paper II). The overall sensitivity of intraoperative frozen section examination with H&E staining was 72.3%, with IHC 72.3% and with IC 48.9%. The accuracy of the three methods was 87.3%, 87.3% and 76.5%, respectively. Combining intraoperative frozen section with H&E staining and IHC raised the sensitivity to 80.9%, whereas the addition of intraoperative IC examination did not affect the results. The sensitivity of intraoperative frozen section for micrometastases was 35% with H&E staining, 45% with MC and 55% with IC (paper II). In a study including 30 patients operated with SNB alone and 30 patients with SNB and axillary clearance (ALND), a comparison was made of the clinical outcome, lymphoscintigraphy of the arm, arm volume, skin circulation and skin temperature, 2-3 years after radiotherapy (paper IV). None of die 30 patients operated with SNB showed any clinical manifestation of lymph oedema. Of the 30 patients operated with ALND, 6 (20%) had clinical lymph oedema, defined as an arm volume increase of more than 10% in the affected arm compared to the nonoperated arm (paper IV). Conclusion: Sentinel node biopsy is feasible and safe in palpable and non-palpable breast cancer and after previous breast biopsy. Sentinel node biopsy can accurately predict the nodal status of the axilla. The intraoperative frozen section analysis of SNB with H&E staining showed an acceptable sensitivity in detecting macrometastases in the lymph node. Lymph drainage in the operated arm and morbidity both seemed to be less affected by SNB than by ALND

Efficient Removal of Polycyclic Aromatic Hydrocarbons and Heavy Metals from Water by Electrospun Nanofibrous Polycyclodextrin Membranes

Here, a highly efficient membrane based on electrospun polycyclodextrin (poly-CD) nanofibers was prepared and exploited for the scavenging of various polycyclic aromatic hydrocarbons (PAHs) and heavy metals from water. The poly-CD nanofibers were produced by the electrospinning of CD molecules in the presence of a cross-linker (i.e., 1,2,3,4-butanetetracarboxylic acid), followed by heat treatment to obtain an insoluble poly-CD nanofibrous membrane. The membrane was used for the removal of several PAH compounds (i.e., acenaphthene, fluorene, fluoranthene, phenanthrene, and pyrene) and heavy metals (i.e., Pb2+, Ni2+, Mn2+, Cd2+, Zn2+, and Cu2+) from water over time. Experiments were made on the batch sorption of PAHs and heavy metals from contaminated water to explore the binding affinity of PAHs and heavy metals to the poly-CD membrane. The equilibrium sorption capacity (qe) of the poly-CD nanofibrous membrane was found to be 0.43 ± 0.045 mg/g for PAHs and 4.54 ± 0.063 mg/g for heavy metals, and the sorption kinetics fitted well with the pseudo-second-order model for both types of pollutants. The membrane could be recycled after treatment with acetonitrile or a 2% nitric acid solution and reused up to four times with similar performance. Further, dead-end filtration experiments showed that the PAH removal efficiencies were as high as 92.6 ± 1.6 and 89.9 ± 4.8% in 40 s for the solutions of 400 and 600 μg/L PAHs, respectively. On the other hand, the removal efficiencies for heavy metals during the filtration were 94.3 ± 5.3 and 72.4 ± 23.4% for 10 and 50 mg/L solutions, respectively, suggesting rapid and efficient filtration of heavy metals and PAHs by the nanofibrous poly-CD membrane

Influence of lifestyle factors on mammographic density in postmenopausal women

BACKGROUND:Mammographic density is a strong risk factor for breast cancer. Apart from hormone replacement therapy (HRT), little is known about lifestyle factors that influence breast density. METHODS:We examined the effect of smoking, alcohol and physical activity on mammographic density in a population-based sample of postmenopausal women without breast cancer. Lifestyle factors were assessed by a questionnaire and percentage and area measures of mammographic density were measured using computer-assisted software. General linear models were used to assess the association between lifestyle factors and mammographic density and effect modification by body mass index (BMI) and HRT was studied. RESULTS:Overall, alcohol intake was positively associated with percent mammographic density (P trend  = 0.07). This association was modified by HRT use (P interaction  = 0.06): increasing alcohol intake was associated with increasing percent density in current HRT users (P trend  = 0.01) but not in non-current users (P trend  = 0.82). A similar interaction between alcohol and HRT was found for the absolute dense area, with a positive association being present in current HRT users only (P interaction  = 0.04). No differences in mammographic density were observed across categories of smoking and physical activity, neither overall nor in stratified analyses by BMI and HRT use. CONCLUSIONS:Increasing alcohol intake is associated with an increase in mammography density, whereas smoking and physical activity do not seem to influence density. The observed interaction between alcohol and HRT may pose an opportunity for HRT users to lower their mammographic density and breast cancer risk

Are elderly and aged asthma different diseases? Results of a multicenter study

28th International Congress of the European-Respiratory-Society (ERS) -- SEP 15-19, 2018 -- Paris, FRANCEGemicioglu, Bilun/0000-0001-5953-4881; aydin, omur/0000-0002-3670-1728; Dursun, A. Berna/0000-0002-6337-6326; GOKSEL, Ozlem/0000-0003-1121-9967WOS: 000455567107243…European Respiratory So

“Sentinel lymph node imaging with sequential SPECT/CT lymphoscintigraphy before and after neoadjuvant chemoradiotherapy in patients with cancer of the oesophagus or gastro-oesophageal junction – a pilot study”

Abstract Background In current best practise, curatively intended treatment for oesophageal cancer usually consists of neoadjuvant chemo-radiotherapy (nCRT) or perioperative chemotherapy, and oesophagectomy. Sentinel Lymph Node Biopsy (SLNB) has the potential to identify patients without lymph node metastases and thus improve the staging accuracy and influence treatment. The impact of neoadjuvant treatment on the lymphatic drainage of oesophageal cancers and subsequently the SLNB procedure in this tumour type has previously not been well studied. Purpose To evaluate changes in lymphatic drainage patterns of the tumour in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) using Sentinel Lymph Node (SLN) hybrid SPECT/CT lymphoscintigraphy before and after nCRT. Methods Patients with clinical stage T2-T3, any N-stage, M0 cancer of the oesophagus or GOJ underwent endoscopically guided peri−/intratumoral injection of radio-colloid followed by hybrid SPECT/CT lymphoscintigraphy prior to, and once again following, nCRT. SPECT/CT images were evaluated to number and location of SLNs and compared between the two examinations. Results Ten patients were included in this pilot trial. SPECT/CT lymphoscintigraphy was performed in twenty procedures. The same Sentinel Lymph Node station before and after nCRT was observed in one single patient. In two patients, no SLN was detected before nCRT. In three patients no SLN was detected following nCRT. In four patients, the SLN stations were not the same station at baseline compared to follow-up examination. Conclusions The reproducibility SLN detection in patients with cancer of the oesophagus/GOJ following nCRT was very poor. nCRT appears to alter lymphatic drainage patterns and thus may affect detection of SLNs and potentially also the accuracy of an SLNB in these patients. On the basis of these initial results, we abort further patient recruitment in our institution. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier ACTRN12618001433291. Date registered: 27/08/2018. Retrospectively registered

Characteristics of the study population, overall and by quartiles of percent density.

<p>Abbreviations: BMI  =  body mass index; OC  =  oral contraceptive; HRT  =  hormone replacement therapy. * In parous women only. † Percentage of women with missing values on age at menarche (9.2%), OC use (0.3%), age at first birth (10.5%) and breastfeeding (11.7%).</p

Age and multivariable adjusted means of mammographic density measures by physical activity.

*<p>Percent density and dense area were square-root transformed for analysis and the values shown are on a back-transformed scale. † In ever smokers only.</p><p>Model 1: adjusted for age at mammography</p><p>Model 2: adjusted for age at mammography, BMI, age at menarche, parity and age at first birth (nulliparous, 1 child age at first birth <25 years, 1 child age at first birth ≥25 years, 2 children age at first birth <25 years, 2 children age at first birth ≥25 years, ≥3 children age at first birth <25 years, ≥3 children age at first birth ≥25 years), age at menopause, OC use (never, ever), HRT use (never, former, current), smoking (never, former, current), alcohol intake (non-drinker, 0,1–4,9 g/day, 5.0–9.9 g/day, ≥10 g/day), and physical activity recent years (never, less than 1 hr per week, 1–2 hrs per week, >2 hrs per week).</p

Age and multivariable adjusted means of mammographic density measures by alcohol intake and smoking habits.

<p>Age and multivariable adjusted means of mammographic density measures by alcohol intake and smoking habits.</p

Multivariable adjusted means of mammographic density measures by alcohol intake, stratified by HRT use.

*<p>Percent density and dense area were square-root transformed for analysis and the values shown are on a back-transformed scale.</p><p>Model 1: adjusted for age at mammography.</p><p>Model 2: adjusted for age at mammography, BMI, age at menarche, parity and age at first birth (nulliparous, 1 child age at first birth <25 years, 1 child age at first birth ≥25 years, 2 children age at first birth <25 years , 2 children age at first birth ≥25 years, ≥3 children age at first birth <25 years, ≥3 children age at first birth ≥25 years), age at menopause, OC use (never, ever), HRT use (never, former, current), smoking (never, former, current), alcohol intake (nondrinker, 0,1–4,9 g/day, 5.0–9.9 g/day, ≥10 g/day), and physical activity recent years (never, less than 1 hr per week, 1–2 hrs per week, >2 hrs per week).</p