Clinical impact of dose overestimation by effective path length calculation in stereotactic ablative radiation therapy of lung tumors

PurposeTo determine the clinical impact of calculated dose differences between effective path length (EPL) and Monte Carlo (MC) algorithms in stereotactic ablative radiation therapy (SABR) of lung tumors.Methods and MaterialsWe retrospectively analyzed the treatment plans and clinical outcomes of 77 consecutive patients treated with SABR for 82 lung tumors between 2003 and 2009 at our institution. Sixty treatments were originally planned using EPL, and 22 using MC. All plans were recalculated for the same beam specifications using MC and EPL, respectively. The doses covering 95%, 50%, and 5% (D95, D50, D5, respectively) of the target volumes were compared between EPL and MC (assumed to be the actual delivered dose), both as physical dose and biologically effective dose. Time to local recurrence was correlated with dose by Cox regression analysis. The relationship between tumor control probability (TCP) and biologically effective dose was determined via logistic regression and used to estimate the TCP decrements due to prescribing by EPL calculations.ResultsEPL overestimated dose compared with MC in all tumor dose-volume histogram parameters in all plans. The difference was >10% of the MC D95 to the planning target volume and gross tumor volume in 60 of 82 (73%) and 52 of 82 plans (63%), respectively. Local recurrence occurred in 13 of 82 tumors. Controlling for gross tumor volume, higher physical and biologically effective planning target volume D95 correlated significantly with local control (P = .007 and P = .045, respectively). Compared with MC, prescribing based on EPL translated to a median TCP decrement of 4.3% (range, 1.2%-37%) and a > 5% decrement in 46% of tumors.ConclusionsClinical follow-up for local lung tumor control in a sizable cohort of patients treated with SABR demonstrates that EPL overestimates dose by amounts that substantially decrease TCP in a large proportion. EPL algorithms should be avoided for lung tumor SABR.     

Excision Repair Cross Complementation Group 1 and Thymidylate Synthase Expression in Patients With Mesothelioma

BackgroundWe hypothesized that in patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), high expression of excision repair cross complementation group 1 (ERCC1) and low expression of thymidylate synthase (TS) are associated with prolonged survival.Patients and MethodsConsecutive patients undergoing EPP at our institutions were reviewed. Tissue microarrays were constructed using five 1-mm cores per patient. TS and ERCC1 protein expression was evaluated by immunohistochemical techniques. The average percentage scores from evaluable cores were assessed and the median score was used to divide the group. Overall survival (OS) from the time of surgery was determined by the Kaplan-Meier method and results were compared by the log-rank test.ResultsEighty patients were included: median age, 58 years; 79% men; 76% epithelial and 24% biphasic subtypes; 25% and pathologic stage I/II and 73% stage III/IV. The median OS was 18.2 months (80% deceased at the censor date). Nineteen patients received neoadjuvant chemotherapy; 2 patients received chemotherapy with adjuvant intent and 28 patients received palliative chemotherapy. The median score was 10.2% for TS and 35% for ERCC1. There was no correlation between TS expression and OS (13.7 vs. 21.6 months for low and high levels, respectively; P = .32). There was a trend between high ERCC1 expression and longer OS (27.6 vs. 10.3 months; P = .06).ConclusionIn this series of patients with MPM undergoing EPP, TS expression was not associated with prolonged survival, but there was a trend for longer survival in patients with high ERCC1 expression.     

Generation and characterization of CD1d‐specific single‐domain antibodies with distinct functional features

Ligation of the CD1d antigen‐presenting molecule by monoclonal antibodies (mAbs) can trigger important biological functions. For therapeutic purposes camelid‐derived variable domain of heavy‐chain‐only antibodies (VHH) have multiple advantages over mAbs because they are small, stable and have low immunogenicity. Here, we generated 21 human CD1d‐specific VHH by immunizing Lama glama and subsequent phage display. Two clones induced maturation of dendritic cells, one clone induced early apoptosis in CD1d‐expressing B lymphoblasts and multiple myeloma cells, and another clone blocked recognition of glycolipid‐loaded CD1d by CD1d‐restricted invariant natural killer T (iNKT) cells. In contrast to reported CD1d‐specific mAbs, these CD1d‐specific VHH have the unique characteristic that they induce specific and well‐defined biological effects. This feature, combined with the above‐indicated general advantages of VHH, make the CD1d‐specific VHH generated here unique and useful tools to exploit both CD1d ligation as well as disruption of CD1d–iNKT interactions in the treatment of cancer or inflammatory disorders.     

Shear bond strength and debonding characteristics of a new premixed self-etching with a reference total-etch adhesive

Background

To determine the shear bond strength and adhesive remnant index of a new premixed self-etching primer and adhesive (Tectosan, BonaDent, Germany) for orthodontic appliances in comparison to a reference total-etch system Transbond XT.

Methods

Bovine incisors were embedded in resin and randomly divided into two groups of 16 samples each. Brackets (Discovery, Dentaurum, Germany) were bonded in group 1 (total-etch-system, Transbond XT) and in group 2 (self-etch-system, Tectosan) with curing light for 40 s. Shear bonding strengths were measured after 24 h of storage in distilled water at 37 °C with a Zwicki 1120 testing machine (Zwick Roell, Germany). A force was applied on the bracket base at the wings in occluso-gingival direction. Then the adhesive remnant index (ARI) was determined.

Results

No statistical differences on SBS were found for both bonding agents (p?=?0.63). ARI scores however differed statistically significantly (p?=?0.035): in the total-etch group more adhesive remained on the teeth, whereas in the self-etch group more adhesive remained on the brackets. There were no visible enamel damages in both groups.

Conclusions

No differences in the shear bond strength were found between both bonding agents. In our study the self-etch-system shifted the adhesive remnant index from more adhesive on the teeth to more adhesive on the bracket - as other already published self-etch systems did - with the new benefit of not increased enamel damages. Tectosan might therefore be a promising alternative to adhesive systems.

     

Experience of pain and analgesia with water and land births

This study aimed to evaluate the pattern and correlates of premenstrual symptomatology amongst Nigerian female undergraduates. Female University students (n = 409) completed questionnaires detailing sociodemographic, menstruation/gynecological history and personality traits. They were then rated with a checklist for premenstrual symptoms. The most frequent premenstrual symptoms were ‘breast tenderness’ (35.5%), ‘sleeplessness’ (15.6%), ‘decreased interest in usual activities' (15.4%), ‘lethargy/easy fatigability/lack of energy’ (13.2%) and ‘change in appetite’ (13.2%). The prevalence of premenstrual symptomatology was 50.1% and the correlates of increasing premenstrual symptomatology included increasing age, increasing severity of menstrual pain, personality traits of neuroticism and agreeableness and increasing body mass index. Although the rate of premenstrual symptomatology in sub-Saharan African women was comparable with that in the western cultures, there may be cross-cultural differences in the pattern of presentation. Dysmenorrhoea and personality traits should be taken into consideration when planning and implementing effective strategy to manage perimenstrual problems in this region.     

Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity?

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA). PLEVA patients only very rarely have systemic signs; the cutaneous lesions are usually asymptomatic, but may be pruritic and may heal with scarring. FUMHD often starts out as classic PLEVA, but goes on to develop widespread ulceronecrotic lesions and is associated with a high mortality rate. Whether Pityriasis lichenoides chronica (PLC) and PLEVA form a spectrum rather than single entities of clonal lymphoproliferative diseases has been discussed. Recently, it has been proposed that FUMHD, too, is a clonal lymphoproliferative disorder. Here, we report two cases of FUMHD with monoclonal T-cell population, as detected by Southern blot analysis. We propose that clonal FUMHD represents a cutaneous T-cell lymphoma entity.     

Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin

BACKGROUND: Cannabinoid receptors mediate the psychopharmacological action of marijuana and have been localized in the central and peripheral nervous system as well as on cells of the immune system. OBJECTIVE: Up to now, two cannabinoid receptors (CB1 and CB2) have been cloned and recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in the skin. METHODS: In the present immunohistochemical investigation we determined the precise localization of CB1 and CB2 in sections of human skin and in one case of mastocytosis. RESULTS: CB1 and CB2 immunoreactivity was observed in cutaneous nerve fiber bundles, mast cells, macrophages, epidermal keratinocytes, and the epithelial cells of hair follicles, sebocytes and eccrine sweat glands. In epidermal keratinocytes, hair follicle and sebaceous glands, CB1 and CB2 were distributed in a complementary fashion. Double-immunostaining with an anti-CGRP antibody suggested the presence of cannabinoid receptors on small afferent peptidergic nerves. CONCLUSION: The abundant distribution of cannabinoid receptors on skin nerve fibers and mast cells provides implications for an anti-inflammatory, anti-nociceptive action of cannabinoid receptor agonists and suggests their putatively broad therapeutic potential.     

Pruritus – Pathophysiologie,Klinik und Therapie – Eine Übersicht

Pruritus is an unpleasant sensory perception of the skin associated with the desire to scratch. As a physiological nociception, pruritus leads to the removal of harmful agents such as parasites and plants from the skin surface. More often, pruritus occurs as a severe and therapy‐refractory symptom of various underlying dermatological and systemic diseases. Comparable to chronic pain, chronic pruritus worsens the general condition and may lead to physical and psychological exhaustion. Until the 1990s, pruritus had been regarded as an incomplete pain sensation. Only recently, itch was defined as a separate, pain‐independent sensation with its own mediators, spinal neurons and cortical areas. These observations led to the development of new therapeutic modalities. This paper gives an overview of itch pathophysiology, clinical types and therapies.