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Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Objectives: To evaluate the long-term anatomical and functional results of myringoplasty in a large cohort of children and analyse factors determining outcome of surgery., Methods: A retrospective analysis of 469 cases of primary and revision pediatric myringoplasties conducted between 2003 and 2018 at the Ghent University Hospital was performed. Anatomical success was defined as an intact tympanic membrane postoperatively. Overall success was defined as an intact tympanic membrane, preservation or improvement of hearing and an ear free from otitis media with effusion, atelectasis, ear discharge and myringitis. The impact of different variables on outcome was investigated by univariate analysis., Results: In primary cases, anatomical success was achieved in 96.8% and 94.3% at early respectively late evaluation (after 1 resp. 12 months). Overall success was achieved in 65.4% and 68.5% at early and late evaluation respectively. In revision cases, early anatomical and overall success were achieved in 96.8% and 53.8%, dropping to respectively 88.9% and 47.1% at late evaluation. In primary cases, presence of bilateral perforations was a significant predictor of a negative anatomical outcome. Further analysis of anatomical, audiological, and overall success rates in primary and revision cases could not withhold any significant predictors., Conclusion: Anatomical success rates of myringoplasty in children are high, in primary as well as revision surgery. When taking the functional status in account however, success rates are lower. The presence of a bilateral perforation predicts a worse outcome with higher anatomical failure rates. No other factors with significant predictive effect on outcome were identified., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We present a case of a patient visiting the ear, nose and throat department with a parotid gland mass, ptosis and facial numbness. CT imaging confirmed a mass in the parotid gland; however, it also revealed a mass in the left maxillary sinus. MRI, positron emission tomography combined with CT and nasal biopsy confirmed the diagnosis of a extranodal natural killer/T cell lymphoma, nasal type. Because this is a rare clinical entity in Western society, patients are typically diagnosed in an advanced stage; symptoms resemble chronic rhinosinusitis and histopathological analysis is challenging. In this atypical case, the patient presented with symptoms of ptosis, parotid gland mass and facial numbness instead of nasal symptoms. In this case, we want to emphasise that diagnosing a sinonasal NK/T-cell lymphoma is often challenging., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe an approach for reporting master protocol research programs (MPRPs) that is consistent with existing good reporting practices and that uses structured information to convey the overall master protocol and design of each substudy., Design: Qualitative analysis., Data Sources: ClinicalTrials.gov trial registry., Main Outcome Measures: Established goals and related practices of the trial reporting system were outlined, examples and key characteristics of MPRPs were reviewed, and specific challenges in registering and reporting summary results to databases designed for traditional clinical trial designs that rely on a model of one study per protocol were identified., Results: A reporting approach is proposed that accommodates the complex study design of MPRPs and their results. This approach involves the use of separate registration records for each substudy within one MPRP protocol (with potential exceptions noted)., Conclusions: How the proposed approach allows for clear, descriptive, structured information about each substudy's prespecified design and supports timely reporting of results after completion of each substudy is described and illustrated. Although the focus is on reporting to ClinicalTrials.gov, the approach supports broader application across trial registries and results databases. This paper is intended to stimulate further discussion of this approach among stakeholders, build awareness about the need to improve reporting of MPRPs, and encourage harmonization across trial registries globally., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: supported, in part, by the National Center for Biotechnology Information and the Intramural Research Program of the National Cancer Institute for the submitted work; RJW, HDD, and TT received support from the National Center for Biotechnology Information of the National Library of Medicine, National Institutes of Health; SDC, DL, GAS, and SAP received support from the Intramural Research Program of the National Cancer Institute, National Institutes of Health; and DAZ received personal fees from ClinicalTrials.gov (and provided technical consultation to ClinicalTrials.gov outside the submitted work); no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: The COVID-19 pandemic posed unprecedented strain on enrollment to cancer clinical trials and their conduct. Here, we highlight an analysis using information from the National Cancer Institute (NCI) Clinical Trials Reporting Program database to describe enrollment patterns to interventional cancer treatment trials at NCI-Designated Cancer Centers during the pandemic. Enrollment to cancer treatment trials at NCI-Designated Cancer Centers decreased precipitously early in the pandemic and has not yet fully returned to the 2019 baseline as of mid-2021. We discuss possible reasons for this and how some of the changes in clinical trial conduct implemented during the pandemic may become part of the standard conduct of NCI-supported clinical trials and broaden access to trials., Competing Interests: Conflicts of Interest and Source of Funding: The data analyses have been supported by the National Cancer Institute, National Institutes of Health, under contract 140D0420F0417. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objective: To evaluate long-term hearing results of stapedotomy and analyze the influence of patient-, disease-, and procedure-related variables., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: 230 ears (202 patients, 10-74 years) underwent stapedotomy for otosclerosis between January 2008 and August 2014. All cases had early postoperative follow-up (4 weeks post-surgery) and 181 cases had late postoperative follow-up (≥ 1 year, average 32.5 months)., Intervention: Stapedotomy procedure for otosclerosis., Main Outcome Measures: Hearing outcome using conventional audiometry. The primary outcome parameter was the postoperative air-bone gap pure-tone average. Postoperative air-bone gap ≤ 10 dB was defined as surgical success. Preoperative, early postoperative and late postoperative hearing results were compared. Influence of patient- and procedure-related variables on hearing outcome was evaluated by logistic regression analysis., Results: The postoperative air-bone gap was 10 dB or less in 77.0% of cases early post-surgery and in 70.7% of cases in long-term follow-up. Air-bone gap closure within 20 dB was obtained in 95.7 and 92.3%, respectively. Logistic regression analysis demonstrated that a larger preoperative air-bone gap (p = 0.041) and positive family history of otosclerosis (p = 0.044) were predictive for less surgical success early postoperatively, but not on the long term. Age, gender, primary versus revision surgery, presence of preoperative tinnitus and preoperative vertigo did not independently and significantly influence postoperative air-bone gap closure., Conclusion: Our series confirms excellent hearing results achieved in stapedotomy surgery, also in long-term follow-up. On the long-term no patient-, disease-, or procedure-related variables were identified as predictors of surgical success.

The given and family names of all the co-authors are incorrect in the published article. The correct names should read as follows.

Low-temperature scanning tunneling microscopy was used to follow the formation of a solvation shell around an adsorbed functionalized azo dye from the attachment of the first water molecule to a fully solvated molecule. Specific functional groups bind initially one water molecule each, which act as anchor points for additional water molecules. Further water attachment occurs in areas close to these functional groups even when the functional groups themselves are already saturated. In contrast, water molecules surround the hydrophobic parts of the molecule only when the two-dimensional solvation shell closes around them. This study thus traces hydrophilic and hydrophobic properties of an organic molecule down to a sub-molecular length scale., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects) . These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/ persistence rates, high morbidity following non-specific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular sub-types of VMs. This incorporated the embryological ongm, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustrated as a separate topic to differentiate from isolated VMs and to rectify the existing confusion with name-based eponyms such as Klippei-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndromebased VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Objective: Acquired atresia of the external auditory canal is a rare condition in which the medial part of the external auditory canal is obliterated by a soft fibrous plug, mostly as a result of chronic inflammation of the outer ear canal. In this study, the clinical and audiometric long-term postsurgical results were assessed., Patients: Records of patients with acquired atresia, surgically treated in a tertiary referral center during the period 2000-2009, were retrospectively reviewed. Preoperative and postoperative clinical and audiometric data were collected., Intervention: All patients underwent the same surgical technique, consisting of a maximal bony canaloplasty with coverage of the bony ear canal using full-thickness skin graft and a meatoplasty. Eligible patients were reinvited for objective and subjective evaluation., Main Outcome Measures: The primary outcome was the long-term postoperative status, based on clinical (patency and condition of the external auditory canal) and audiometric findings (mean air-bone gap)., Results: The analysis comprised 17 operated ears (14 different patients). Mean follow-up time was 5.14 years. True recurrence occurred in 3 ears (17.6%), whereas another 4 ears had episodic otorrhea (23.5%). At early (<0.5 yr), but also at late follow-up (>4y), the air-bone gap in the operated ears was significantly smaller., Conclusion: Surgical treatment for acquired atresia leads to beneficial results. Patients should be informed of the possibility of recurrence of disease. Nevertheless, they seem to be satisfied with the surgical intervention. Preoperative dermatologic referral is required, given the high prevalence of an underlying dermatologic disease.

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects). These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/persistence rates, high morbidity following nonspecific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular subtypes of VMs. This incorporated the embryological origin, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustratedas a separate topic to differentiate from isolated VMs and to rectify the existing confusion with namebased eponyms such as Klippel-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndrome-based VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

Patients with congenital vascular malformations often suffer from arthralgia, especially of the lower limbs. This orthopaedic disease pattern is defined as destructive, angiodysplatic arthritis or Hauert disease and leads to very early destruction of the joints. By presenting diagnostic and therapeutic algorithms, Hauert disease is emphasized as a possible differential diagnosis in order to minimize the risk of an incorrect diagnosis which might lead to under-, over-, or even incorrect treatment. A minimally invasive transathroscopic therapy in the early stages can lead to significant improvement of symptoms and prevention of progressive joint destruction.

We examined bile acid transport and expression of the apical sodium-dependent bile acid transporter (ASBT) in ileal preparations to determine if alterations in bile acid excretion contributed to a hypercholesterolemia-resistant phenotype in rabbits (CRT/mlo). Taurocholate transport was not different between normal (NR) and CRT/mlo rabbits fed regular diet. However, feeding cholesterol-enriched diet reduced taurocholate transport significantly in CRT/mlo rabbits (0.53 + or - 0.06 pmol/microg protein) compared to regular diet (0.95 + or - 0.14 pmol/microg protein), but had no effect in NR rabbits. Cholesterol-enriched diet increased ASBT mRNA in CRT/mlo (2.6 + or - 0.7 to 5.4 + or - 0.1); no significant changes occurred in NR. Some CRT/mlo rabbits carry a polymorphism in ASBT at amino acid 333 (P333L). In transfected HEK293 cells, TC transport of P333L allele was significantly lower (0.08 + or - 0.01 vs 0.13 + or - 0.01 pmol/microg protein/15 sec, P< 0.05). This allele was not found in NR rabbits. The data suggest that the phenotype of the CRT/mlo rabbit is due to changes in bile acid transport as well as bile acid metabolism.

Cancer patients mount adaptive immune responses against their tumor. However, while tumor-infiltrating lymphocytes and natural-killer (NK) cells try to detect and eliminate malignant cells, they eventually fail when these malignant cells develop mechanisms to evade effective immunosurveillance. First, malignant cells produce immunosuppressive cytokines and prostaglandins that skew the immune response toward a Th2 response, resulting in a humoral response with significantly less antitumor capacities, generating a low interleukin-2 environment blocking NK cell division, T-helper cell proliferation, and T-cytotoxic cell proliferation and function. Second, immunoresistant malignant cell variants emerge through selection of major histocompatibility class I and II and antigen-processing mutants reducing antigenicity. Finally, malignant cells may actively eliminate T-cells via activation-induced cell death or by mounting a counterattack through Fas ligand expression.

Background: The appearance of natural suppressor cells and circulating endothelial progenitor cells in tumour tissue has been associated with myelopoetic stimulation by growth factors that may increase fluorodeoxyglucose (FDG) uptake by the bone marrow and high FDG uptake by bone marrow in patients suffering from human malignancies is a not uncommon finding., Methods: This study looked at the relationship between bone marrow FDG uptake, biochemical (Hb level, RBC count, WBC count and platelet count), clinical and radiological findings and outcome in a series of 35 patients suffering from squamous cell carcinoma of the head and neck (SCCHN), consecutively referred for FDG PET as part of their routine staging procedure., Results and Conclusion: In SCCHN, mean FDG standardized uptake values (SUVs) of the primary tumour correlate significantly with blood WBC count (r=0.44; P=0.011, Bonferroni corrected P=0.04) and mean FDG SUVs of bone marrow are significantly correlated to the maximum FDG SUVs of the primary tumour (r=0.523; P=0.002). Finally, FDG uptake by the bone marrow is related to disease-free and overall survival. These findings warrant confirmation in a larger patient series.

Introduction: Information obtained on the IL-2 receptor status of tumour infiltrating lymphocytes in patients suffering from squamous cell carcinoma of the head and neck (SSCHN) before and after IL-2 treatment may lead to a better understanding of the immunological changes and related kinetics induced at the tumour level and ultimately to a strategy that allows selection of those patients that will benefit from IL-2 therapy. This study set out to assess the relationship between (123)I-IL2 single-photon emission computed tomography (SPECT) findings and the presence of IL-2 receptors (CD25 staining) on tumour-infiltrating lymphocytes as well as on SCCHN tumour cells in patients suffering from SCCHN., Materials and Methods: Seventeen consecutive patients (12 men; mean age, 57 years) highly suspected to suffer from SSCHN were prospectively included in the study. All patients underwent planar and whole body (123)I-IL2 scintigraphy and underwent surgery or had a biopsy taken within 1 week from imaging. Surgical resected primary lesions as well as biopsy material from primary tumours were histologically analysed with respect to the presence and intensity of CD25 expression on tumour infiltrating lymphocytes and tumour cells (HSCORE). Tumor-to-background (T/N) ratios of the primary tumour derived from planar and tomographic (123)I-IL2 scintigraphy were related to the results derived from histology., Results: All patients suffered from SSCHN. T/N ratios derived from SPECT images were significantly correlated with CD25 lymphocyte HSCOREs (r = 0.66; p = 0.03), but not with CD25 tumour cell HSCOREs., Conclusions: (123)I-IL-2 SPECT imaging allows for non-invasive imaging of the relative amount of IL-2 receptors present on tumour infiltrating lymphocytes in SCCHN.

Purpose: The purpose of the study was to report on the prognostic value of (99m)Tc-hydrazinonicotinamide (HYNIC) Annexin-V single-photon emission computed tomography (SPECT) imaging in patients suffering from primary squamous cell carcinoma of the head and neck., Methods: Twenty-nine patients diagnosed with a primary untreated head and neck squamous cell carcinoma were included in this study. In all patients, (99m)Tc-HYNIC Annexin-V scintigraphy SPECT was performed before treatment instigation. Tumour-to-background ratios (T/N) of the primary tumour, derived from reconstructed images, as well as clinical variables were obtained in all patients and related to patient outcome. Median follow-up was 22.6 months (range 4.1-55.8 months)., Results: On univariate as well as multivariate analysis, only the (99m)Tc-HYNIC Annexin-V T/N ratio dichotomized using the group median as cutoff value (T/N ratio of 2) was predictive of recurrence-free survival (respectively, p = 0.0000 and 0.000). On univariate analysis, only lymph node status dichotomized according to N0 vs N1-N2-N3 disease and the (99m)Tc-HYNIC Annexin-V T/N ratio dichotomized using the group median as cutoff value (T/N ratio of 2) were predictive of overall survival (p = 0.0051 and 0.0000). When both factors were included in the multivariate model, both N status and the (99m)Tc-HYNIC Annexin-V T/N ratio showed an independent association with overall survival (p = 0.001 for lymph node status and 0.000 for dichotomized (99m)Tc-HYNIC Annexin-V T/N ratio)., Conclusion: (99m)Tc-HYNIC Annexin-V T/N ratios derived from SPECT provides independent prognostic information on disease-free survival and overall survival.

Aim: The aim of this study was to report on the relationship between preradiotherapy and prechemotherapy 99mTc-HYNIC Annexin-V tumor uptake values, reflecting ongoing apoptosis, and outcome to radiotherapy and/or chemotherapy., Methods: Twenty-three cancer patients underwent staging examinations and a 99mTc-HYNIC Annexin-V scintigraphy and subsequent radiotherapy and/or chemotherapy. Tumor-to-background ratios derived from tomographic 99mTc-HYNIC Annexin-V images were related to treatment outcome as assessed by RECIST criteria., Results: Six patients underwent radiotherapy or radiochemotherapy: 4 exhibited response to treatment, 1 had stable, and 1 progressive disease. Corresponding tumor-to-background ratio's were respectively >or=2.3 (in responders), 1.2 in the patient presenting with stable disease and 1 in the patient presenting with progressive disease. Seventeen patients were treated by chemotherapy alone: 8 were progressive, 1 patient presented with stable disease and 8 responded to treatment. In 1/8 progressive patients a tumor-to-background ratio of 1.4 was found, the others showed no uptake. In the patient presenting with stable disease a ratio of 0.1 was found. In the 8 responders, 7 patients had a tumor-to-background ratio >or=1.3 whereas in 1 patient a ratio of 0.3 was found. Tumor-to-background ratios in responders (complete plus partial) (median 2.5, range: 0.3-4.2) were significantly higher when compared to those obtained in non-responders (stable plus progressive disease) (median 1, range: 0.1-1.4) (P<0.001)., Conclusion: The findings presented suggest that 99mTc-HYNIC Annexin-V pretreatment uptake may be useful to predict response to chemo- and radiotherapy.

This study reports on the relationship between quantitative (99m)Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary ( n, number of patients=22) or locally recurrent ( n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and (99m)Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following (99m)Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of (99m)Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images correlated linearly with FasL HSCORES( r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images and MMP-9 HSCORES, MVD or the number of tumour-infiltrating lymphocytes. MVD correlated significantly with MMP-9 HSCORES ( r=0.44, P=0.03).

Because of its potential to allow for noninvasive, repetitive, and selective in vivo identification of the site and extent of apoptotic cell death and for monitoring cell death kinetics without the need for invasive biopsy, radiolabeled annexin-V is of major clinical relevance. This paper reviews available preclinical and clinical data on radiolabeled annexin-V pertaining to the domain of monitoring response to radiotherapy and chemotherapy, focusing especially on advantages and drawbacks of the different labeling procedures for the radiolabeling of annexin-V.

In this study, the potential of 99mTc-HYNIC Annexin-V scintigraphy to visualize primary head and neck carcinoma was assessed and compared with computed tomography (CT) findings and histology. Eighteen patients suspected of having primary head and neck carcinoma underwent a spiral CT scan and 99mTc-HYNIC Annexin-V scintigraphy within 1 week of each other, followed by resection of the suspected lesion. Results obtained by CT and scintigraphy were compared vs. histopathology. The diagnosis was primary head and neck carcinoma in 18 patients, accompanied by lymph node involvement in seven patients. 99mTc-HYNIC Annexin-V uptake was identified in five patients on planar images and in 17 patients on tomographic images (single-photon emission computed tomography, SPECT), corresponding to the pathological regions identified by CT. In the remaining patient, CT and 99mTc-HYNIC Annexin-V scintigraphy were false negative. In 11 patients, SPECT and CT scan were concordant, identifying all primary lesions and two sites of lymph node involvement. In the six remaining patients, CT and SPECT accurately identified the primary lesion, but were discordant with regard to the existence of lymph node involvement. In five of six patients, SPECT failed to identify lymph node involvement, whereas CT scan did not. In the remaining patient, CT scan was false positive for lymph node involvement, whereas SPECT was not. In this series, 99mTc-HYNIC Annexin-V allowed for the visualization of all primary head and neck tumours identified by CT scan, but failed to identify most of the sites of lymph node involvement.

This article reviews the literature on the use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and thallium-201, technetium-99m sestamibi and technetium-99m tetrofosmin single-photon emission tomography (SPET) for the diagnosis and staging of primary and recurrent squamous cell carcinoma of the head and neck (SCCHN). A search of the MEDLINE and CancerLit databases covering articles entered between 1989 and February 2003 was performed. In the case of FDG PET, only full-ring PET studies that included comparison with conventional morphological imaging were considered. Due to the wide variation in methodology, a straightforward meta-analysis of FDG PET literature was impossible. Instead, indicative summary receiver-operating curves of FDG PET and morphological imaging techniques were generated and a paired comparison of the sensitivities and specificities of FDG PET and morphological imaging performed. Compared with conventional morphological imaging, FDG PET proved as sensitive and specific for the detection of primary SCCHN but more sensitive and specific for the detection of cervical lymph node involvement (CLNI) and recurrence of SCCHN. Additional studies addressing the role of FDG PET in screening for distant metastases and synchronous primary tumours are mandatory. Following negative conventional evaluations, FDG PET identifies occult primary tumours in 20-50% of patients presenting with CLNI. As regards the use of 201Tl, 99mTc-sestamibi and 99mTc-tetrofosmin, more studies are required to define whether these imaging agents could form part of the current diagnostic armamentarium in SCCHN patients. It is concluded that FDG PET either is superior to or offers added value when compared with conventional morphological imaging techniques for the purpose of diagnosis and staging of primary and recurrent SCCHN.

On the basis of the Hamburg Classification from 1988 six different therapeutic tactics and surgical techniques have been proved in the treatment of vascular malformations. These are: 1) reconstructive surgery, 2) surgery to reduce the hemodynamic activity of the vascular defect, 3) surgery to extirpate the malformed vessels, 4) combined therapy, 5) unconventional therapy, 6) multidisciplinary treatment. More than 2500 cases had been worked out. In this survey the marginal vein and the embryonal vein respectively are of special interest. These veins are classified by morphologic radiologic criteria. The following types could be worked out: peripheral type, thigh type and pelvic type. Referring to these experiences the indications for vascular surgical treatment have to be distinguished precisely. In a retrospective European study the long follow-up results of all six therapeutic tactics had been registered and proved. 1378 cases were included. In 15% of the patients the results were excellent in 42% good, and in 34% an improvement could be observed. In 5% a relapse was stated and in 1.5% no change was registered.

Background: Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/min has been shown in patients with PAOD III/IV to significantly improve healing of trophic lesions, relief of rest pain, and reduce the rate of major amputation or death at 6 months as compared to placebo. The effect is considered related to improvement of the microcirculation. The aim of the present trial was to identify an optimum dose regarding treatment response and tolerability, by studying 4 doses of 25, 50, 75 and 100 micrograms iloprost daily., Patients and Methods: 302 patients with PAOD IV were randomised via a double-blind fashion to one of the 4 doses. The primary endpoint was the responder rate at end of treatment. Responders were defined as patients with very good or good global efficacy, as judged by lesion healing and pain relief. Side effects were documented and a pre-defined benefit/risk index was calculated., Results: No dose-dependency of iloprost regarding primary or secondary endpoints was observed. The rate of responders ranged between 48.7-53.5%. Side effects, mainly related to vasodilation, increased dose-dependently (p < 0.001, chi 2-test), with a significant decrease of the benefit/risk index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA). Responders had a better outcome at 6 months than non-responders (2.6 fold higher rate of major amputation or death; life table analysis)., Conclusions: It is concluded that iloprost should be titrated to the optimum rather than maximum tolerated dose, since a higher incidence of side effects not associated with an increased treatment response was observed at higher doses.

Congenital AV shunting defects are not as rare as sometimes presumed, and they are four times more frequent in girls than in boys. Inadequate treatment can aggravate the patient's complaints by increasing the circulatory disturbance in the affected region. As a result, ischemic ulceration may develop. Special, usually interdisciplinary, treatment of such findings is mandatory. When AV communications are present, the combined treatment of surgical and nonsurgical techniques must be considered. Location and pathoanatomic type influence this choice. Clinical, functional, and hemodynamic parameters must also be evaluated in order to decide the optimal combination of therapeutic measures. Usually several phases of treatment are necessary.

Incidence, etiology, diagnostic procedures and therapy of venous aneurysms, basing on 152 own cases, are discussed. The main procedure for diagnosis is phlebography. It must be distinguished between aneurysms of epi- and subfascial veins. The localization determines the surgical procedure which represents the only successful therapy. Without proper treatment, venous aneurysms may be responsible for complications such as thrombophlebitis, thrombosis with pulmonary embolism, aneurysm rupture and compression of adjacent structures. The results of surgical treatment are excellent.