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Radiotherapy (RT) target volume concepts for locally advanced lung cancer have been under discussion for years. Although they may be as important as treatment doses, many aspects of them are still based on conventions, which, due to the paucity of prospective data, rely on long-term practice or on clinical knowledge and experience (e.g., on patterns of spread or recurrence). However, in recent years, large improvements have been made in medical imaging and molecular imaging methods have been implemented, which are of great interest in RT. For lung cancer, in recent years, 18F-fluoro-desoxy-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) has shown a superior diagnostic accuracy as compare to conventional imaging and has become an indispensable standard tool for diagnostic workup, staging and response assessment. This offers the chance to optimize target volume concepts in relation to modern imaging. While actual recommendations as the EORTC or ESTRO-ACROP guidelines already include imaging standards, the recently published PET-Plan trial prospectively investigated conventional versus imaging guided target volumes in relation to patient outcome. The results of this trial may help to further refine standards. The current review gives a practical overview on procedures for pre-treatment imaging and target volume delineation in locally advanced non-small cell lung cancer (NSCLC) in synopsis of the procedures established by the PET-Plan trial with the actual EORTC and ACROP guidelines.

Radiotherapy (RT) target volume concepts for locally advanced lung cancer have been under discussion for years. Although they may be as important as treatment doses, many aspects of them are still based on conventions, which, due to the paucity of prospective data, rely on long-term practice or on clinical knowledge and experience (e.g., on patterns of spread or recurrence). However, in recent years, large improvements have been made in medical imaging and molecular imaging methods have been implemented, which are of great interest in RT. For lung cancer, in recent years, 18F-fluoro-desoxy-glucose (FDG)positron-emission tomography (PET)/computed tomography (CT) has shown a superior diagnostic accuracy as compare to conventional imaging and has become an indispensable standard tool for diagnostic workup, staging and response assessment. This offers the chance to optimize target volume concepts in relation to modern imaging. While actual recommendations as the EORTC or ESTRO-ACROP guidelines already include imaging standards, the recently published PET-Plan trial prospectively investigated conventional versus imaging guided target volumes in relation to patient outcome. The results of this trial may help to further refine standards. The current review gives a practical overview on procedures for pre-treatment imaging and target volume delineation in locally advanced non-small cell lung cancer (NSCLC) in synopsis of the procedures established by the PET-Plan trial with the actual EORTC and ACROP guidelines.

Objectives To investigate whether breast MRI has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Methods Forty-seven patients were included. All had undergone both breast MRI and dedicated axillary MRI, followed by surgery. All included breast MRI exams had complete field of view (FOV) of the axillary region. First, unenhanced T2-weighted (T2W) and subsequent diffusion-weighted (DW) images of both MRI exams were independently analyzed by two breast radiologists using a confidence scale and compared to histopathology. ADC values were measured by two researchers independently. Diagnostic performance parameters were calculated on a patient-by-patient basis. Results T2W breast MRI had the following diagnostic performance: sensitivity of 50.0% and 62.5%, specificity of 92.3%, PPV of 57.1% and 62.5%, NPV of 90.0% and 92.3%, and AUC of 0.72 for reader 1 and 0.78 for reader 2. T2W dedicated axillary MRI had the following diagnostic performance: sensitivity of 37.5% and 62.5%, specificity of 82.1% and 92.3%, PPV of 44.6% and 50.0%, NPV of 87.8% and 91.4%, and AUC of 0.65 for reader 1 and 0.73 for reader 2. In both evaluations, addition of DW images resulted in comparable diagnostic performance. For both breast MRI and dedicated axillary MRI, there was no significant difference between mean ADC values of benign and malignant lymph nodes. Conclusions T2W breast MRI with complete FOV of the axillary region has comparable diagnostic performance as T2W dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Optimization of T2W breast MRI protocol by including a complete FOV of the axillary region can, therefore, be recommended in clinical practice. Key Points • Breast MRI with complete field of view of the axillary region has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. • Optimization of breast MRI protocol by including a complete field of view of the axillary region is recommended in clinical practice. • For both breast MRI and dedicated axillary MRI, DW imaging (including ADC measurements) is of no added value.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. Objective: To present the results from the APCCC 2019. Design, setting, and participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naive prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. Results and limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.

Most vaccines developed today include only the antigens that best stimulate the immune system rather than the entire virus or microbe, which makes vaccine production and use safer and easier, though they lack potency to induce acceptable immunity and long-term protection. The incorporation of additional immune stimulating components, named adjuvants, is required to generate a strong protective immune response. Nucleic acids (DNA and RNA) and their synthetic analogs are promising candidates as vaccine adjuvants activating Toll-like receptors (TLRs). Additionally, in the last few years several nanocarriers have emerged as platforms for targeted co-delivery of antigens and adjuvants. In this review, we focus on the recent developments in polymer nanomaterials presenting nucleic acids as vaccine adjuvants. We aim to compare the effectiveness of the various classes of polymers in immune modulating materials (nanoparticles, dendrimers, single-chain particles, nanogels, polymersomes and DNA-based architectures). In particular, we address the critical role of parameters such as size, shape, complexation and release of TLR ligands, cellular uptake, stability, toxicity and potential importance of spatial control in ligand presentation.

OBJECTIVE: The objective of the study was to determine the parameters that can be used to predict malignancy in persistent cervical lymphadenopathies. METHODS: We retrospectively reviewed the files of 162 patients diagnosed with persistent cervical lymphadenopathy who underwent an excisional biopsy in our department between January 2011 and October 2019. Patient demographics and the size, side, duration, and localization of lymphadenopathy were recorded, and their relationship with histopathological results was investigated. Multiple regression analysis was used to determine the relationship between clinical parameters and malignancy. RESULTS: Of the 162 patients, 91 (56.2%) were male and 71 (43.8%) were female, and the mean age was 45.40 +/- 20.41 (2-84) years. Male gender (OR=3.099; p=0.003), increasing age (OR=1.029; p=0.002), short duration of lymphadenopathy (OR=0.989; p=0.048), and neck level V (OR=2.604; p=0.031) patients had a statistically significantly higher risk of malignancy. There was no statistically significant relationship between the side and size of the lymph node and the risk of malignancy (p>0.05). CONCLUSION: In our study, male gender was determined to be the most predictive risk factor for malignancy in patients with cervical lymphadenopathy, followed by lymph node neck level, increased age, and duration of the disease.

Literature reports increased FDG nodal uptake in HIV-positive patients. Our aim is to identify differences in presentation and characteristics of FDG-avid lymph nodes between HIV-positive and HIV-negative locally advanced cervical cancer (LACC) patients in our clinical setting. We evaluated 250 pre-treatment 18F-FDG PET/CT imaging studies from women screened for a phase III randomised controlled trial investigating modulated electro-hyperthermia as a radiosensitiser (Ethics approval: M120477). The number of nodes, size, maximum standardised uptake value (SUVmax), symmetry, and relationship between nodal size and SUVmax uptake, were assessed by region and by HIV status. In total, 1314 nodes with a SUVmax ≥ 2.5 were visualised. Of 128(51%) HIV-positive participants, 82% were on antiretroviral therapy (ART) and 10 had a CD4 count four nodes visualised in the neck, symmetrical inguinal lymph nodes, increased rates of supraclavicular node visualisation, FDG-avid axillary nodes were more common, but not exclusive, in HIV-positive participants. 18F-FDG PET/CT is a reliable staging method for LACC in HIV-positive patients who are not in acute stages of HIV infection, have a CD4 count &gt, 200 cells/µL, and/or are on ART and there is a potential risk of underestimating metastatic spread by attributing increased nodal metabolic activity to HIV infection in these patients.

Background The optimal extent of groin completion lymph node dissection (CLND) (inguinal or ilioinguinal dissection) in patients with melanoma is controversial. The aim of this study was to evaluate whether the extent of groin CLND after a positive sentinel node biopsy (SNB) is associated with improved outcome. Methods Data from all sentinel node‐positive patients who underwent groin CLND at four tertiary melanoma referral centres were retrieved retrospectively. Baseline patient and tumour characteristics were collected for descriptive statistics, survival analyses and Cox proportional hazards regression analyses. Results In total, 255 patients were included, of whom 137 (53·7 per cent) underwent inguinal dissection and 118 (46·3 per cent) ilioinguinal dissection. The overall CLND positivity rate was 18·8 per cent; the inguinal positivity rate was 15·5 per cent and the pelvic positivity rate was 9·3 per cent. The pattern of recurrence, and 5‐year melanoma‐specific survival, disease‐free survival and distant‐metastasis free survival rates were similar for both dissection types, even for patients with a positive CLND result. Cox regression analysis showed that type of CLND was not associated with disease‐free or melanoma‐specific survival. Conclusion There was no significant difference in recurrence pattern and survival rates between patients undergoing inguinal or ilioinguinal dissection after a positive SNB, even after stratification for a positive CLND result. An inguinal dissection is a safe first approach as CLND in patients with a positive SNB., Inguinal is enough

Purpose. Repeat sentinel node biopsy (SNB) is an alternative to axillary lymph node dissection (ALND) for axillary staging in recurrent breast cancer. This study was conducted to determine factors associated with technical success of repeat SNB.Methods. A total of 536 patients with locally recurrent nonmetastatic breast cancer underwent lymphatic mapping (LM) and repeat SNB in 29 Dutch hospitals.Results. A total of 179 patients previously underwent breast-conserving surgery (BCS) with SNB, 262 patients BCS with ALND and 61 patients mastectomy, 35 with SNB and 26 with ALND. Another 34 patients underwent breast surgery without axillary interventions. A repeat sentinel node (SN) was identified in 333 patients (62.1 %) and was successfully removed in 235 (53.5 %). The overall repeat SN identification rate was 62.1 %, varying from 35 to 100 % in the participating hospitals. Previous radiotherapy of the breast [odds ratio (OR) 0.16; 95 % confidence interval (CI) 0.03-0.84], subareolar tracer injection (OR 0.34; 95 % CI 0.16-0.73), and a 2-day LM protocol (OR 0.57; 95 % CI 0.33-0.97) after previous BCS were independently associated with failure of SN identification. Injection of a larger amount of tracer (>180 MBq) led to a higher identification rate (OR 4.40; 95 % CI 1.45-13.32).Conclusions. Repeat SNB is a technically feasible procedure for axillary staging in recurrent breast cancer patients. Previous radiotherapy appears to be associated with failure of SN identification. Injection with a larger amount of tracer (>180 MBq) leads to a higher identification rate; subareolar injection and a 2-day LM protocol after previous BCS appear to be less adequate.

Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the small GTPase Cdc42 and other effectors, these proteins participate in the remodelling of the actin network downstream of BCR engagement. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination. These defects were found, at least in part, to be intrinsic to the B cell compartment. In vivo, ITSN2 deficient B cells show a reduction in the expression of SLAM, CD84 or ICOSL that correlates with a diminished ability to form long term conjugates with T cells, to proliferate in vivo, and to differentiate into germinal centre cells. In conclusion, our study not only revealed a key role for ITSN2 as an important regulator of adaptive immune-response during vaccination and viral infection but it is also likely to contribute to a better understanding of human immune pathologies.

Purpose To evaluate the diagnostic performance of unenhanced axillary T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) imaging for axillary nodal staging in patients with newly diagnosed breast cancer, with node-by-node and patient-by-patient validation. Materials and Methods Institutional review board approval and informed consent were obtained. Fifty women (mean age, 60 years; range, 22-80 years) underwent high-spatial-resolution axillary 3.0-T T2-weighted imaging without fat suppression and DW imaging (b = 0, 500, and 800 sec/mm2), followed by either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection. Two radiologists independently scored each lymph node on a confidence level scale from 0 (benign) to 4 (malignant), first on T2-weighted MR images, then on DW MR images. Two researchers independently measured the mean apparent diffusion coefficient (ADC) of each lymph node. Diagnostic performance parameters were calculated on the basis of node-by-node and patient-by-patient validation. Results With respective node-by-node and patient-by-patient validation, T2-weighted MR imaging had a specificity of 93%-97% and 87%-95%, sensitivity of 32%-55% and 50%-67%, negative predictive value (NPV) of 88%-91% and 86%-89%, positive predictive value (PPV) of 60%-70% and 62%-75%, and area under the receiver operating characteristic curve (AUC) of 0.78 and 0.80-0.88, with good interobserver agreement (kappa = 0.70). The addition of DW MR imaging resulted in lower specificity (59%-88% and 50%-84%), higher sensitivity (45%-64% and 75%-83%), comparable NPV (89% and 90%-91%), lower PPV (23%-42% and 34%-60%), and lower AUC (0.68-0.73 and 0.70-0.86). ADC measurement resulted in a specificity of 63%-64% and 61%-63%, sensitivity of 41% and 67%, NPV of 85% and 85%-86%, PPV of 18% and 35%-36%, and AUC of 0.54-0.58 and 0.69-0.74, respectively, with excellent interobserver agreement (intraclass correlation coefficient, 0.83). Conclusion Dedicated high-spatial-resolution axillary T2-weighted MR imaging showed good specificity on the basis of node-by-node and patient-by-patient validation, with good interobserver agreement. However, its NPV is still insufficient to substitute it for SLNB for exclusion of axillary lymph node metastasis. DW MR imaging and ADC measurement were of no added value. (c) RSNA, 2014.

In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3′-deoxy-3’L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated melanoma to molecular changes within the tumor. We will be able to correlate both 18F-FDG and 18F-FLT PET to outcome and decide on the best modality to predict long-term remissions to combined BRAF/MEK-inhibitors. Results coming from this study may help in identifying responders from non-responders early after the initiation of therapy and reveal early development of resistance to vemurafenib/cobimetinib. Furthermore, we believe that the results can be fundamental for further optimizing individual patient treatment. Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils or dendritic cells and their effect does not rely on local macrophage depletion nor does it depend upon Toll-like receptor signaling or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as a novel class of adjuvants that boost humoral immune responses.

Axillary staging in patients with locally recurrent breast cancer is important for obtaining locoregional control and predicting prognosis. The aim of the present study is to determine technical feasibility, validity, aberrant drainage patterns and clinical consequences of performing repeat sentinel node biopsy (SNB) in these patients. We performed a systematic review and meta-analysis of the literature and included all studies on repeat SNB in locally recurrent breast cancer. A total of 692 patients were described, 301 after a previous SNB, 361 after a previous axillary lymph node dissection (ALND), and 30 with no previous axillary surgery. Sentinel node identification was successful in 452 of the 692 patients (65.3 %), which was significantly higher in patients who had undergone previous SNB compared to previous ALND (81.0 vs. 52.2 %) (P

Background and purpose Advanced lung cancer patients experience anatomical changes during radiotherapy. Uncorrected, these may lead to lower tumor dose, but can be corrected for by adaptive radiotherapy (ART). Material and methods Anatomical changes in 233 patients were monitored online on cone-beam CT-scans used for daily soft-tissue matching. If systematic changes above the pre-defined trigger criteria were observed, a new CT-scan, delineations, and treatment plan were made, restoring the intended dose distribution. Dose distributions with and without adaptation were compared. The first fifty ART patients were given two surveillance CT-scans during radiotherapy. These were used to evaluate delivered dose for patients without adaptation. The first fifty-two patients treated with ART were also compared with 52 pre-ART patients to evaluate the reduction in normal tissue doses. Results Sixty-three patients (27%) were adapted. Seventy-five per cent of all adaptations correctly adjusted for a decrease in tumor dose. Eighty-seven surveillance CT-scans were obtained for the first fifty patients and in only 2% of the cases, a decrease in tumor coverage (ΔV95%CTV > 1%) was observed. With ART we observed a significant decrease in lung dose (MLD reduced from 14.6 Gy to 12.6 Gy on average). Conclusions Implementation of soft-tissue match combined with ART decreased the lung dose. The trigger criteria used correctly identified all but one (98%) of the patients requiring adaptation with a false positive rate of 20%.

BACKGROUND Historically, blue dyes, (99)Tc or a combination of the two tracers have been used for sentinel lymph node (SLN) mapping in cervical and endometrial cancer patients. Indocyanine green (ICG), as a tracer, has been recently introduced in this setting. Our goal was to assess the differences in overall and bilateral detection rates as well as in false-negative rates among the different tracers. METHODS The electronic databases PubMed, MEDLINE, and Scopus were searched in January 2016 by searching the terms "sentinel lymph node" and "dye" and "indocyanine green," and "cervical cancer" or "endometrial cancer." Series comparing different tracers injected intracervically and reporting the detection rate and/or SLN false-negative rate were selected. RESULTS Forty-five studies were retrieved. Six studies including 538 patients met selection criteria. Compared with blue dyes, ICG SLN mapping had higher overall (odds ratio [OR] 0.27; 95 % confidence interval [CI] 0.15-0.50; p

Early diagnosis of TB is essential for community health and infection control, as well as for starting appropriate therapy for patients. Early detection of MDR is essential for the same reasons, plus the fact that currently a very high percentage of MDR patients die, especially in developing countries. Both genotypic and phenotypic methods allowing assessment of MDR tuberculosis on the bacilli isolated from fluids of infected patients are available, but these tests are lengthy (6-16 weeks) and require infected body fluids, which are not always easily assessable. Patients presenting pulmonary TB can also be culture-negative. Diagnosis of active disease in a pulmonary tuberculoma has long been problematic because the non-specific character of the disease, its changing manifestations and the slow growth of the organisms make its isolation a long and time-consuming process. Determination of pulmonary tuberculoma activity may be mandatory for optimal treatment strategy, therefore imaging techniques may be helpful in early detection. The aim of this review is to assess the role of Positron Emission Tomography (PET) imaging in the diagnosis and therapy management of TB. Although studies and data on the potential role of FDG PET in the diagnosis of tuberculosis are limited, a literature search revealed some interesting studies on this subject. Most of the studies described indicate that PET imaging, especially FDG PET as diagnostic tool, could be a noninvasive method that gives additional information about the disease status, enabling improved therapeutic management of pulmonary mycobacterial infection. Furthermore, several studies provide evidence that PET imaging could be useful in tuberculostatic therapy evaluation.

High VEGFC mRNA expression of acute myeloid leukemia (AML) blasts is related to increased in vitro and in vivo drug resistance. Prognostic significance of VEGFC on long-term outcome and its associated gene expression profiles remain to be defined. We studied effect of VEGFC on treatment outcome and investigated gene expression profiles associated with VEGFC using microarray data of 525 adult and 100 pediatric patients with AML. High VEGFC expression appeared strongly associated with reduced complete remission rate (P = .004), reduced overall and event-free survival (OS and EFS) in adult AML (P = .002 and P < .001, respectively). Multivariable analysis established high VEGFC as prognostic indicator independent of cytogenetic risk, FLT3-ITD, NPM1, CEBPA, age, and white blood cell count (P = .038 for OS; P = .006 for EFS). Also, in pediatric AML high VEGFC was related to reduced OS (P = .041). A unique series of differentially expressed genes was identified that distinguished AML with high VEGFC from AML with low VEGFC, that is, 331 up-regulated genes (representative of proliferation, vascular endothelial growth factor receptor activity, signal transduction) and 44 down-regulated genes (eg, related to apoptosis) consistent with a role in enhanced chemoresistance. In conclusion, high VEGFC predicts adverse long-term prognosis and provides prognostic information in addition to well-known prognostic factors.

Purpose of reviewIn early-stage vulvar, cervical and endometrial cancer, lymph node status is the most important prognostic factor. Surgical treatment is aimed at removing the primary tumor and adequately staging the regional lymph nodes. As morbidity of regional lymphadenectomy is high, sentinel node biopsy is a technique with potential for I adequate staging with less treatment-related morbidity. This manuscript reviews its current role in vulvar, cervical and endometrial cancer.Recent findingsIn early-stage vulvar cancer, level 3 evidence indicates that it appears to be safe to omit inguinofemoral lymphadenectomy in case of a negative sentinel node. However, false-negative results with fatal consequences do occur and are often attributable to procedural failures. For early-stage cervical cancer, level 3 evidence points to an acceptable false-negative rate of a negative sentinel node; clinical utility and safety remain to be established. The optimal technique of the sentinel node biopsy in endometrial cancer is currently unclear.SummaryIn early-stage vulvar cancer, data suggest that sentinel node biopsy could be offered as a treatment option instead of routine inguinofemoral lymphadenectomy. However, more (long-term follow-up) data are needed to further appreciate real clinical benefits. It is emphasized that the procedure should be performed by a skilled multidisciplinary team, centralized in oncology centers and preferably within the protection of clinical trials. For cervical cancer, data are promising, but routine application cannot be recommended due to lack of data on clinical utility and safety. For endometrial cancer, studies on the sentinel node biopsy are still in feasibility stage.

Background: Sentinel lymph node biopsy is an established staging method in early breast cancer. After a negative biopsy, most institutions will not perform a completion axillary dissection. The present study reports the current axillary recurrence (AR) rate, overall and disease-free survival in the Swedish Multicenter Cohort Study. Methods: From 3534 patients with primary breast cancer

The aim of this study was to assess the diagnostic performance of F-18-FDG PET and integrated F-18-FDG PET/CT for diagnosing recurrent esophageal cancer after initial treatment with curative intent. Methods: The PubMed, Embase, and Cochrane library were systematically searched for all relevant literature using the key words "F-18-FDG PET" and "esophageal cancer" and synonyms. Studies examining the diagnostic value of F-18-FDG PET or integrated F-18-FDG PET/CT, either in routine clinical follow-up or in symptomatic patients in whom recurrence of esophageal cancer was suspected, were deemed eligible for inclusion. The primary outcome was the presence of recurrent esophageal cancer as determined by histopathologic biopsy or clinical follow-up. Risk of bias and applicability concerns were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Sensitivities and specificities of individual studies were meta-analyzed using bivariate random-effects models. Results: Eight eligible studies were included for meta-analysis, comprising 486 patients with esophageal cancer who underwent F-18-FDG PET or PET/CT after previous treatment with curative intent. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable; there were few concerns with regard to the risk of bias and applicability. Integrated F-18-FDG PET/CT and standalone F-18-FDG PET were used in 4 and 3 studies, respectively. One other study analyzed both modalities separately. In 4 studies, F-18-FDG PET or PET/CT was performed as part of routine follow-up, whereas in 4 other studies the diagnostic test was performed on indication during clinical follow-up. Pooled estimates of sensitivity and specificity for F-18-FDG PET and PET/CT in diagnosing recurrent esophageal cancer were 96% (95% confidence interval, 93%-97%) and 78% (95% confidence interval, 66%-86%), respectively. Subgroup analysis revealed no statistically significant difference in diagnostic accuracy according to type of PET scanner (standalone PET vs. integrated PET/CT) or indication of scanning (routine follow-up vs. on indication). Conclusion: F-18-FDG PET and PET/CT are reliable imaging modalities with a high sensitivity and moderate specificity for detecting recurrent esophageal cancer after treatment with curative intent. The use of F-18-FDG PET or PET/CT particularly allows for a minimal false-negative rate. However, histopathologic confirmation of F-18-FDG PET-or PET/CT-suspected lesions remains required, because a considerable false-positive rate is noticed.

Background: Lymphedema of the upper extremity is a common side effect of lymph node dissection or irradiation of the axilla. Several techniques are being applied in order to examine the presence and severity of lymphedema. Measurement of circumference of the upper extremity is most frequently performed. An alternative is the water-displacement method. The aim of this study was to determine the reliability and the reproducibility of the Inverse Water Volumetry apparatus (IWV-apparatus) for the measurement of arm volumes. Patients and Methods: The IWV-apparatus is based on the water-displacement method. Measurements were performed by three breast cancer nurse practitioners on ten healthy volunteers in three weekly sessions. Results: The intra-class correlation coefficient, defined as the ratio of the subject component to the total variance, equaled 0.99. The reliability index is calculated as 0.14kg. This indicates that only changes in a patient's arm volume measurement of more than 0.14kg would represent a true change in arm volume, which is about 6% of the mean arm volume of 2.3kg. Conclusion: The IWV-apparatus proved to be a reliable and reproducible method to measure arm volume.

© 2015 Macmillan Publishers Limited. All rights reserved.Foxp3+ regulatory T cells (Tregs) maintain immune homoeostasis through mechanisms that remain incompletely defined. Here by two-photon (2P) imaging, we examine the cellular dynamics of endogenous Tregs. Tregs are identified as two non-overlapping populations in the T-zone and follicular regions of the lymph node (LN). In the T-zone, Tregs migrate more rapidly than conventional T cells (Tconv), extend longer processes and interact with resident dendritic cells (DC) and Tconv. Tregs intercept immigrant DCs and interact with antigen-induced DC:Tconv clusters, while continuing to form contacts with activated Tconv. During antigen-specific responses, blocking CTLA4-B7 interactions reduces Treg-Tconv interaction times, increases the volume of DC:Tconv clusters and enhances subsequent Tconv proliferation in vivo. Our results demonstrate a role for altered cellular choreography of Tregs through CTLA4-based interactions to limit T-cell priming.

In 2008, the first Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V) showed that omission of inguinofemoral lymphadenectomy is safe in patients with early-stage vulvar cancer and a negative sentinel node and it simultaneously decreases treatment-related morbidity. An important part of the sentinel node procedure is pathologic ultrastaging of the removed sentinel nodes. Subsequently, since the introduction of this procedure in the standard care of patients with early-stage vulvar cancer, more and smaller inguinofemoral lymph node metastases have been diagnosed. The clinical consequences of these micrometastases are not clear yet. With increasing size of the sentinel node metastasis, chances of non-sentinel node metastases increase and those of survival decrease. The size of lymph node metastases is included in the latest staging system for vulvar cancer, however at this moment without clinical implications. Furthermore, a separate category for micrometastases is not incorporated yet. More research is needed to determine the clinical consequences of the size of (sentinel) lymph node metastases. (C) 2015 Elsevier Ltd. All rights reserved.

Background: We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma. Methods: Patients with a primary cutaneous melanoma were randomly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred, or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy. Results: Among 1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for death, 0.74; 95% confidence interval [CI], 0.59 to 0.93; P=0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor-positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P

Background: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients.Methods: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis.Results: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively.Conclusion: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.

BACKGROUND. The potential of positron emission tomography (PET) with F-18-fluoro-2-deoxy-D-glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor.METHODS. Twenty-nine patients with various histologic types of metastases from an unknown primary site were studied after unsuccessful conventional diagnostic workup. The patients received 370 megabecquerels (MBq) (10 millicuries) FDG intravenously and whole body scans were made after 30 minutes after injection onward.RESULTS, All but one known metastatic tumor sites were visualized. Additional metastases were discovered in five patients. With FDG-PET the primary tumor was identified in 7 patients (24%): in 2 patients with carcinoma of the nasopharynx, in I patient with plasmacytoma of the base of the tongue, in 1 patient with carcinoma of the lung, in 1 patient with carcinoma of the colon, and in 2 patients with breast carcinoma. FDG-PET did not identify a primary tumor in the remaining 22 patients (76%). Despite a negative PET study, the primary lesion was identified in a later phase in 3 of these patients (14%). Survival was not altered by discovery of the primary tumor.CONCLUSIONS. A previously unknown primary turner was able to be identified with FDG-PET in 7 of 29 patients after an unsuccessful conventional diagnostic workup. However, the clinical relevance of PET information in this setting is limited. (C) 1998 American Cancer Society.

The work of the author AL is funded by The Royal College of Surgeons of Edinburgh Robertson’s Trust, The Melville Trust for the care and cure of cancer and The Medical Research Council Scottish Clinical Pharmacology and Pathology Programme. The work of authors FCO, JN, ACPR, DJH and GDS mentioned above is funded by the Chief Scientist Office, grant number ETM37, and supported by Chief Scientist Funded Health Sciences Scotland and the Cancer Research UK Experimental Cancer Medicine Centre. Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly, this work highlights the need for further pathway analysis of metastatic tumours for overcoming drug resistance and developing new therapies. Publisher PDF

Squamous cell carcinoma (SCC) of the buccal mucosa is an aggressive form of oral cancer. It tends to spread to adjacent tissues and often metastasizes to occult cervical node. There are multiple techniques for cheek reconstruction after tumor removal, including temporalis myocutaneous and temporoparietal fascial pedicled flaps and a forearm free flap. In this report, a case of a 76-year-old man with SCC of the left cheek mucosa and extending to the posterolateral superior alveolar ridge is presented. The patient underwent radical excision of the tumor, omolateral modified radical neck dissection (MRND-III), and contralateral selective neck dissection (levels I-III). Reconstruction was performed with a facial artery myomucosal free flap. The flap was transplanted successfully, and there were no donor or recipient site complications. This technique is a good reconstructive option because of its adherence to the plastic surgery principle of "replacing like with like" and its minimal donor-site morbidity.

Amac: Bu calismada, doku biyopsileri ile ince igne aspirasyonu (IIA) karsilastirildi ve bu kombinasyonun mediastinoskopideki yanlis negatiflik oranini azaltip azaltmayacagi arastirildi. Ca­lis­ma­ pla­ni:­Ocak 2004 ve Ekim 2005 tarihleri arasinda servikal video mediastinoskopi uygulanan kucuk hucreli disi akciger kanserli (KHDAK) 92 hasta bu prospektif calismaya dahil edildi. Ayni lenf nodundan hem doku biyopsisi hem de IIA yapildi ve patolojik incelemeye gonderildi. Doku ornekleri ve IIA’lar Hematoksilen-Eosin ile boyandi. Tum ornekler iki histopatolog tarafindan incelendi. Bul gu lar: Doku biyopsisi ornekleri ile 54 hastada metastaza rastlanmaz iken, 38 hastada metastaz saptandi. IIA’da ise 48 hastada metastaza rastlanmaz iken, 44 hastada metastaz saptandi. Farklilik istatistiksel olarak anlamli degil idi (p>0.05). Yanlis negatiflik oranlari, IIA ve doku biyopsisi sonrasi sirasiyla %5.4 ve %12 idi. Negatif IIA ve doku biyopsili 43 hastaya takiben torakotomi ile akciger rezeksiyonu ve total sistematik lenf nodu diseksiyonu yapildi. Mediastinal lenf nodu diseksiyonu sonrasi iki olguda (%4.6) lenf nodu metastazi saptandi. Buna bagli olarak iki yontem kombine edildiginde mediastinoskopinin yanlis negatifligi %4.6’ya indi. Teknige bagli herhangi bir komplikasyon ile karsilasilmadi. So­nuc:­Mediastinal lenf nodlarinin IIA’si doku biyopsisi ile karsilastirildiginda guvenli ve etkili bir yontem olup, doku biyopsisi ile kombine edildiginde mediastinoskopinin yanlis negatiflik oranini azaltabilir. Anah tar soz cuk ler: Biyopsi; ince igne aspirasyonu; akciger kanseri; lenf nodu; mediastinoskopi. Background:­This study aims to compare tissue biopsy with fine needle aspiration (FNA) and investigate whether the combination reduces false negativity of mediastinoscopy. Methods: Between January 2004 and October 2005, 92 patients with non-small cell lung cancer (NSCLC) who underwent cervical video mediastinoscopy were included in this prospective study. Tissue biopsy samples and FNAs were obtained from the same lymph node and were sent for a pathologic examination. Tissue samples and FNAs were stained with Hematoxilene-Eosine. All specimens were evaluated by two histopathologists. Results:­ Using tissue biopsy samples, no metastasis was found in 54 patients, while 38 patients were metastatic. Forty-eight patients had no metastasis, while 44 patients were metastatic using FNA samples. The difference was statistically non-significant (p>0.05). The false negativity of the FNA and tissue biopsy were 5.4% and 12%, respectively. Subsequently, 43 patients with negative FNA and tissue biopsy underwent lung resection with thoracotomy and sistematic lymph node dissection. Following lymph node dissection, lymph node metastases were found in two cases (4.6%). As a result, false negativity of mediastinoscopy was reduced to 4.6% when two techniques were combined. There was no complication related to the technique. Conclusion:­ The FNA of mediastinal lymph nodes is a safe and effective method, compared to tissue biopsy and reduces the false negativity of mediastinoscopy when combined with tissue biopsy.

Shoulder complaints and functional impairment are common sequelae of neck dissection. This is often attributed to injury of the spinal accessory nerve by dissection or direct trauma. Nevertheless, shoulder morbidity may also occur in cases in which the spinal accessory nerve has been preserved. In this article, the physiology and patho-physiology of the shoulder are discussed, followed by a consideration of the impact of neck dissection on shoulder complaints, functional impairment, and quality of life. Finally, rehabilitation will be considered.

Contains fulltext : 81172.pdf (Publisher’s version ) (Closed access) PURPOSE OF REVIEW: In early-stage vulvar, cervical and endometrial cancer, lymph node status is the most important prognostic factor. Surgical treatment is aimed at removing the primary tumor and adequately staging the regional lymph nodes. As morbidity of regional lymphadenectomy is high, sentinel node biopsy is a technique with potential for adequate staging with less treatment-related morbidity. This manuscript reviews its current role in vulvar, cervical and endometrial cancer. RECENT FINDINGS: In early-stage vulvar cancer, level 3 evidence indicates that it appears to be safe to omit inguinofemoral lymphadenectomy in case of a negative sentinel node. However, false-negative results with fatal consequences do occur and are often attributable to procedural failures. For early-stage cervical cancer, level 3 evidence points to an acceptable false-negative rate of a negative sentinel node; clinical utility and safety remain to be established. The optimal technique of the sentinel node biopsy in endometrial cancer is currently unclear. SUMMARY: In early-stage vulvar cancer, data suggest that sentinel node biopsy could be offered as a treatment option instead of routine inguinofemoral lymphadenectomy. However, more (long-term follow-up) data are needed to further appreciate real clinical benefits. It is emphasized that the procedure should be performed by a skilled multidisciplinary team, centralized in oncology centers and preferably within the protection of clinical trials. For cervical cancer, data are promising, but routine application cannot be recommended due to lack of data on clinical utility and safety. For endometrial cancer, studies on the sentinel node biopsy are still in feasibility stage.

Background: We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma. Methods: Patients with a primary cutaneous melanoma were randomly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred, or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy. Results: Among 1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for death, 0.74; 95% confidence interval [CI], 0.59 to 0.93; P=0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor-positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P

Axillary lymph node dissection (ALND) is an important tool in staging patients with breast cancer. However, this procedure has several sequelae and complications and improvement in early diagnosis has led to an increasing number of cases of ALND in which axillary nodes are found to be negative. Sentinel node (SN) biopsy appears to be a less invasive alternative to ALND. The aim of the present study was to assess whether SN is a reliable indicator for axillary staging. We studied 126 consecutive patients with T1-T2 breast cancer and clinically negative axilla. In each case, 30–70 MBq of 99mTC-labelled colloidal albumin was injected subdermally close to the tumour and SN was visualised by lymphoscintigraphy. Surgery was performed 24 h after injection and the SN was removed under the guidance of a gamma ray-detecting probe. ALND was then undertaken in all cases. A histopathologic examination of the SNs was then made and the findings compared with the status of the other axillary nodes. SNs were identified and biopsied in 115/126 patients (91.3%) and correctly predicted the axillary status in 110/115 cases (95.6%). In five cases (4.4%), SNs were found to be negative, but other axillary nodes were positive. Our data confirm that SN biopsy is a good method for staging the axilla in patients with breast cancer. However, before SN biopsy can replace ALND in daily clinical practice, some technical aspects must be standardized, and clinical trials are required in order to clarify the prognostic impact of false-negative cases.