Allergy and Clinical Immunology

Immunization of cats to induce neutralizing antibodies against Fel d 1, the major feline allergen in human subjects

Publication date: Available online 2 May 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Franziska Thoms, Gary T. Jennings, Melanie Maudrich, Monique Vogel, Stefanie Haas, Andris Zeltins, Regina Hofmann-Lehmann, Barbara Riond, Jonas Grossmann, Peter Hunziker, Antonia Fettelschoss-Gabriel, Gabriela Senti, Thomas M. Kündig, Martin F. Bachmann

Background

Cat allergy in human subjects is usually caused by the major cat allergen Fel d 1 and is found in approximately 10% of the Western population. Currently, there is no efficient and safe therapy for cat allergy available. Allergic patients usually try to avoid cats or treat their allergy symptoms.

Objective

We developed a new strategy to treat Fel d 1–induced allergy in human subjects by immunizing cats against their own major allergen, Fel d 1.

Methods

A conjugate vaccine consisting of recombinant Fel d 1 and a virus-like particle derived from the cucumber mosaic virus containing the tetanus toxin–derived universal T-cell epitope tt830-843 (CuMV_TT) was used to immunize cats. A first tolerability and immunogenicity study, including a boost injection, was conducted by using the Fel-CuMV_TT vaccine alone or in combination with an adjuvant.

Results

The vaccine was well tolerated and had no overt toxic effect. All cats induced a strong and sustained specific IgG antibody response. The induced anti–Fel d 1 antibodies were of high affinity and exhibited a strong neutralization ability tested both in vitro and in vivo. A reduction in the endogenous allergen level and a reduced allergenicity of tear samples, were observed.

Conclusion

Vaccination of cats with Fel-CuMV_TT induces neutralizing antibodies and might result in reduced symptoms of allergic cat owners. Both human subjects and animals could profit from this treatment because allergic cat owners would reduce their risk of developing chronic diseases, such as asthma, and become more tolerant of their cats, which therefore could stay in the households and not need to be relinquished to animal shelters.

Graphical abstract

Mepolizumab in patients with eosinophilic granulomatosis with polyangiitis

Publication date: Available online 2 May 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Sergey Moiseev, Eugenia Zagvozdkina, Viktoria Kazarina, Nikolai Bulanov, Pavel Novikov

Cysteine and hydrophobic residues in CDR3 serve as distinct T-cell self-reactivity indices

Publication date: Available online 30 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Stephen R. Daley, Hui-Fern Koay, Kerry Dobbs, Marita Bosticardo, Rushika C. Wirasinha, Francesca Pala, Riccardo Castagnoli, Jared H. Rowe, Lisa M. Ott de Bruin, Sevgi Keles, Yu Nee Lee, Raz Somech, Steven M. Holland, Ottavia M. Delmonte, Debbie Draper, Sandra Maxwell, Julie Niemela, Jennifer Stoddard, Sergio D. Rosenzweig, Pietro Luigi Poliani

Bagels and LOX in Eosinophilic Esophagitis

Publication date: Available online 30 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Netali Ben Baruch-Morgenstern, Tetsuo Shoda, Marc E. Rothenberg

Tamoxifen restores extracellular trap formation in neutrophils from patients of chronic granulomatous disease, in ROS-independent manner

Publication date: Available online 27 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Atul Sharma, Katelyn McCann, Jitendra Kumar Tripathi, Pooja Chauhan, Christa Zerbe, Bibhuti B. Mishra, Steven M. Holland, Jyotika Sharma

HLA and immune-mediated adverse drug reactions: another hit with vancomycin

Publication date: Available online 25 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Munir Pirmohamed

Pollutants in the workplace: Impact on occupational asthma

Publication date: Available online 25 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Kevin J. Kelly, Jill A. Poole

Genomic Interactions with Exposure to Inhaled Pollutants

Publication date: Available online 25 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Stephanie J. London, Erik Melén

Evidence for an IL-6 high asthma phenotype in asthma patients of African ancestry

Publication date: Available online 25 April 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Steven R. White, Bharathi Laxman, Edward T. Naureckas, D.Kyle Hogarth, Julian Solway, Anne I. Sperling, Carole Ober

Oral Surgery, Oral Medicine, Oral Pathology ,Oral Radiology

Using rare diseases as teaching models to increase awareness Publication date: Available online 1 May 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Faizan Alawi

MIGRATION OF THE ROOT COMPLEX AFTER CORONECTOMY OCCURS WITHIN THE FIRST YEAR AFTER SURGERY. A 5-YEAR RADIOGRAPHIC ANALYSIS AND PROTOCOL SUGGESTION Publication date: Available online 27 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Mads Hagen Pedersen, Louise Hauge Matzen, Louise Hermann, Sven Erik Nørholt Abstract Objectives No study exists evaluating the radiographic follow-up protocol after coronectomy. This study aims to assess root migration after coronectomy of mandibular third molars in panoramic images one, three and five years after surgery. Study Design This was a prospective cohort study of patients undergoing coronectomy of a mandibular third molar. The patients followed a five-year follow-up regimen with a panoramic examination at one, three and five years after the surgical intervention. Three observers assessed the panoramic images in a blinded randomized order evaluating bone coverage; superimposition of roots and mandibular canal; and migratory changes of the roots. Descriptive statistics were used to describe changes. Furthermore, reproducibility among the observers was calculated. Results Sixty-two patients were included. Ingrowth of bone superior to the root complex during the first year was registered by all observers (observer 1 100%, observer 2 77.4% and observer 3 85.5%). Superimposition of the mandibular canal and the root complex at the post-surgical panoramic images and after one year showed that 53.2-62.9% went from superimposition to no superimposition. Inter-observer reproducibility was high. Conclusions Migration of the root complex occurs primarily within the first year after coronectomy. Therefore, a routine radiographic follow-up after one year only is recommended.

Therapeutic efficacy of propranolol for infantile hemangiomas Publication date: Available online 26 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Wenli Wu, Hongtao Wang, Jiansuo Hao, Zijun Gao, Fan Li, Yiyang Chen Abstract Objectives This study retrospective analyzes the clinical therapeutic efficacy of propranolol for patients with infantile hemangiomas (IH). Study design Patients with IH were treated with propranolol (2–4.5 mg/kg/day). Those patients who did not have a good response to propranolol underwent intertumoral injection of pingyangmycin or surgery. Results Relative therapeutic responses to propranolol among the 51 patients were 31.37% (16/51) excellent, 39.21% (20/51) good, 23.53% (12/51) poor, and 3.92% (3/51) non-responsive. Of the 15 patients who had a poor or no response to propranolol, two then received injected pingyangmycin and three had surgical resection; the remaining 10 patients received no further therapy. The relevance of many clinical factors (gender, age, dose, depth, and diameter) to the efficacy of propranolol was assessed with univariate and multivariate ordinal logistic regression models, indicating that young (≤ 5 months) age was significantly associated with better efficacy (P ˂ 0.05). The most common side effect was diarrhea (52.2%). There was no significant association between dose of propranolol and side effects (P = 0.12). Conclusions The effect of oral propranolol was better in younger patients. A 3–4.5 mg/kg/day dose might not be better than the conventional recommended dose of 2–3 mg/kg/day.

TMJ Total Joint Replacement using the Zimmer Biomet Microfixation patient fitted prosthesis results in reduced pain and improved function Publication date: Available online 26 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Alero Boyo, Julia McKay, Gerald Lebovic, David J. Psutka Abstract Objective To evaluate the pain and maximum incisal opening (MIO) of patients treated with the Zimmer Biomet Microfixation patient fitted alloplastic temporomandibular joint (TMJ) prosthesis. Methods The authors implemented a retrospective cohort study of patients who had undergone bilateral or unilateral TMJ total joint replacement (TJR). The primary outcome variables were pain and MIO which were measured at various time points between 12 months to over 60 months. Secondary outcomes included perceived masticatory efficiency and patient satisfaction. Results A total of 33 patients (62 joints) met inclusion criteria for the study. The relationship between time and the change in pain scores, although significant immediately after surgery in an unadjusted model, was not statistically significant in an adjusted model. A statistically significant improvement between time and MIO is noted in both adjusted and unadjusted models. A majority of patients (91%) reported a subjective improvement in their diet. Similarly, 91% of patients felt that TJR was beneficial and in retrospect, would repeat their decision to undergo TJR. Conclusion Patients treated with the Zimmer Biomet Microfixation patient fitted TMJ prosthesis experience improvements in their pain, MIO and ability to masticate. Future studies are needed to assess long-term outcomes prospectively.

Risk factors for caries development in Primary Sjogren's Syndrome Publication date: Available online 26 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Nicola Berman, Frederick Vivino, Joshua Baker, Jonathan Dunham, Andres Pinto Abstract Objectives To compare risk factors for caries between SS (primary SS) and non-Sjogren's Syndrome (NSS) salivary hypofunction subjects, and to identify the prevalence of incisal or cervical/root caries in each group. Study Design This was a retrospective, cross-sectional study conducted at a single site between 2012 and 2015 for assessment of subjects with possible SS. Two-hundred and twenty-five (225) subjects (99 SS and 126 NSS) participated in the study Results T-tests and Wilcoxon rank sum tests evaluated group differences in continuous variables and, chi-squared tests determined differences in categorical variables. Significant univariate associations were further assessed using multivariate ordinal regression models. SS were more likely to have a greater number of total caries [OR 1.72 (1.03, 2.88) p=0.04], a focus score ≥ 1/ 4 mm2 was associated to greater number of total caries [OR 2.88 (1.05, 7.93) p=0.04]. Adjusted analysis for salivary flow did not yield a significant association between stimulated or unstimulated, or glandular specific flow and total number of carious lesions. Conclusion Subjects with salivary hypofunction secondary to SS do have a greater caries risk compared to subjects with salivary hypofunction due to other causes. In this cohort, this finding was not associated to salivary flow rates.

Investigation of foreign materials in gingival lesions: A clinicopathologic, energy-dispersive microanalysis of the lesions and in vitro confirmation of pro-inflammatory effects of the foreign materials Publication date: Available online 20 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Leticia Ferreira, Hsin-Hsin Peng, Darren P. Cox, David W. Chambers, Avni Bhula, John D. Young, David M. Ojcius, Erivan S. Ramos-Junior, Ana Carolina Morandini Abstract Objectives This study aimed to evaluate the clinical and histopathological features of gingival lesions containing foreign material (GLFM). In parallel, the composition of the foreign material and its effects in primary human gingival fibroblasts (HGF) were investigated. Study Design Eighty six GLFM were retrieved from an oral pathology biopsy service. Clinical and microscopic data were analyzed and the composition of the particles was identified by energy-dispersive x-ray spectroscopy (EDX). Furthermore, HGF were stimulated with silica (SiO2) microparticles to investigate the production of COL-1, MMP2, and inflammatory cytokines. Results GLFM were most commonly found in women (60.5%) and most frequently described as white plaques. Histopathological examination identified verrucous hyperplasia in 59% and epithelial dysplasia in 28% of the cases. EDX microanalysis revealed that Si (94%) was the most frequently detected foreign element. SiO2 micro-particles induced higher COL-1 expression, higher levels of pro-inflammatory cytokines such as IL-6, IL-8 and TGF-ß, and increased MMP-2 activity in HGF. Conclusion There was a strong association between the presence of foreign material in gingiva and white verrucous clinical lesions. In addition, the most common element in the foreign material was Si, and our in vitro findings demonstrate the importance of silica-mediated effects on gingival fibroblasts.

Changes in condylar dimensions in temporomandibular joints with disc displacement Publication date: Available online 20 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Bo-Yeon Seo, Jung-Sub An, Min-Seok Chang, Kyung-Hoe Huh, Sug-Joon Ahn ABSTRACT Objectives To investigate the condylar dimensions of the temporomandibular joint (TMJ) with respect to disc displacements and gender using computed tomography (CT) and magnetic resonance imaging (MRI). Study Design Disc displacements were divided into three groups based on MRI: normal disc position (NR), disc displacement with reduction (DDR), and disc displacement without reduction (DDNR). After the angular and linear condylar dimensions were calculated from CT images, differences in condylar dimensions with respect to disc displacements and gender were analyzed with two-way analysis of variance. Results Condylar depth and condylar height were significantly smaller in condyles with DDNR than those with NR or DDR (NR = DDR > DDNR). Condylar width gradually decreased significantly from NR to DDNR (NR > DDR > DDNR). The anterior condylar angle was significantly larger in condyles with NR than those with DDR or DDNR (NR > DDR = DDNR). Condyles with DDNR exhibited significantly larger horizontal condylar angles than those with NR or DDR (NR = DDR < DDNR). Altered condylar dimensions associated with disc displacement were not significantly different between men and women. Conclusion Condylar dimensions may be significantly associated with disc displacements of the TMJ, irrespective of gender.

Data Management Practices of CBCT Volumes: An Exploratory User Survey Publication date: Available online 17 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Dwight D. Rice, Kenneth Abramovitch, Gregory W. Olson, Edwin L. Christiansen Abstract Objective To query CBCT users about their storage and transfer practices: to identify trends in the handling of CBCT data in dentistry. Study Design A computer-based survey was distributed to two CBCT user groups. The survey consisted of eighteen questions including: settings for data capture, data storage, archiving strategies, bit depth/compression, monitoring user access to patient information, and dissemination to end users. All information was anonymously collected. Descriptive data and frequency patterns were collected and discussed. Results A total of 68 surveys were returned with 56 fully completed. Results reflected a low consensus about usage and management of radiographic data sets. Some preferential usage patterns however were noted along with the following trends; a. 53% of respondents utilized DICOM volumetric data sets for initial storage. b. 46% of respondents save data in raw, or native file formats. c. 60% of storage sites were in onsite servers. d. 35% of volumes saved were in a "Zip" compression format. e. 37% of respondents used PACS systems for storage. Conclusion The absence of consensus on post-capture management of volumetric data sets underscores that a dentistry-wide data management standard would benefit patient care while mitigating IT storage issues.

ADHERENT WHITE PLAQUES IN A NONSMOKER Publication date: Available online 17 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Andres Flores-Hidalgo, Alice E. Curran

Full blood counts are not predictive of the risk of medication-related osteonecrosis of the jaws: a case-control study. Publication date: Available online 17 April 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Kelly McGowan, Robert S Ware, Caroline Acton, Saso Ivanovski, Newell W Johnson ABSTRACT Objectives The role of immune function in susceptibility to medication-related osteonecrosis of the jaws (MRONJ) remains unclear. This study investigated whether full blood counts, as a measure of systemic health and immune function, predict the development of MRONJ. Study Design A case-control study was conducted in Brisbane, Australia. 57 cases diagnosed with MRONJ from January 2010 to March 2017 were identified from hospital records and individually matched with up to 4 controls using primary disease, sex, age and antiresorptive therapy (total sample = 249). Demographic and clinical data were extracted and associations were investigated using conditional logistic regression. Results 67% of cases and 65% of controls reported at least one result outside of the laboratory reference range (OR=0.7; 95%CI: 0.3, 1.5; p=0.29). The most commonly reported abnormal results were low haemoglobin (53% of cases, 48% of controls) and low haematocrit (33% of cases, 25% of controls). There were no significant differences between groups in any of the reported parameters. Conclusions Patients taking antiresorptive medications frequently return blood test results outside the standard laboratory reference range. Altered blood counts were not limited to patients who developed MRONJ and do not appear to be clinically useful in identifying patients at high risk for this condition.

Current Problems

Information for Readers Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s):

A six-microRNA signature predicts survival of patients with uterine corpus endometrial carcinoma Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Yue Wang, Mu Xu, Qing Yang Abstract Uterine corpus endometrial carcinoma (UCEC) is one of the most common female gynecological malignant tumors that threaten women health seriously. MicroRNAs (miRNAs) has been proved to play critical roles in tumor pathogenesis and malignant progression. In this study, we aimed to explore a novel signature of microRNA expression for predicting the overall survival (OS) of patients with UCEC. The genome-wide miRNA expression profiles and relevant clinical characteristics of 348 patients with UCEC were downloaded from the Cancer Genome Atlas (TCGA) data portal and analyzed comprehensively. A total of 144 miRNAs were confirmed to be expressed differentially in tumor tissues. Among them, 6 miRNAs (hsa-mir-15a.MIMAT0000068, hsa-mir-142.MIMAT0000433, hsa-mir-142.MIMAT0000434, hsa-mir-3170.MIMAT0015045, hsa-mir-1976.MIMAT0009451, and hsa-mir-146a.MIMAT0000449) were validated to be significantly correlated with the OS of patients with UCEC. The risk indictor established by the 6-microRNA signature was proved be an independent prognostic factor (Hazard ratio = 0.391; 95% CI: 0.195-0.783; P = 0.008). In conclusion, we identified miRNAs that were correlated with the occurrence and progression of UCEC and established a 6-microRNA expression signature as a predictor for the OS of patients with UCEC.

Causal effect of obesity on gynecologic malignancies Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Courtney Griffiths, Edward Jimenez, Eva Chalas Abstract Introduction Gynecologic malignancies are estimated to affect 110,070 women and will be the cause of death in approximately 32,120 in 2018. Endometrial cancer is among the most prevalent with 63,320 estimated new cases and approximately 11,350 deaths, followed by ovarian cancer with an estimate of 22,000 new cases and 14,000 deaths annually. Obesity is one of the most modifiable risk factors. Providers should engage in a multifaceted approach to patient education and healthcare to decrease the projected cases of obesity-related cancers. Background The literature demonstrates a significant link between obesity and the development of certain malignancies such as endometrial, pancreatic, and renal cancer. Specific mechanisms found to play a role in the development of these malignancies include alterations of the metabolic pathway attributed to lipid accumulation as well as a chronic inflammatory process. Obesity also predisposes patients to other medical comorbidities as well as a poorer prognosis once a diagnosis of cancer is established. Factors contributing to poorer prognosis include challenges with treatment planning, specifically pertaining to inappropriate chemotherapy dosing and delivery of radiation therapy. Surgical approach and perioperative management are similarly challenging in obese patients and are associated with increased risk of complications. Conclusion Obesity is a modifiable factor which is associated with an increased risk of cancer and poorer outcomes. Providers should educate patients on all health hazards of obesity, including increased risk of cancer, and encourage them to participate in a structured weight loss plan.

Comparison of CA125, HE4, and ROMA index for ovarian cancer diagnosis Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Lei Zhang, Ying Chen, Ke Wang Abstract Objective In view of the high rate of misdiagnosis of ovarian cancer, our study aimed to compare the performances of serum levels of human epididymis secretory protein 4 (HE4) and cancer antigen 125 (CA125), as well as ROMA index in the diagnosis of ovarian cancer. Methods Three hundred and seventy-three patients who suffered ovarian cancer were selected in Tianjin Medical University Cancer Institute and Hospital from July 2016 to July 2017. Patients were divided into premenopause group and postmenopause group. Based on the results of pathologic examinations, patients were divided into malignant, benign, and borderline groups, which were further divided into different pathologic type groups. HE4 and CA125 serum levels in each patient were detected and the ROMA index was analyzed. ROC curve analysis was conducted to compare the performances of serum CA125, serum HE4, and ROMA index in the diagnosis of ovarian cancer. Results Proportion of postmenopausal patients in malignant group (65.2%) was significantly higher than that in the benign group (34.3%). Serum levels of CA125 and HE4, and ROMA index were higher in patients with different types of malignant tumor than those in corresponding benign group. Serum HE4, serum CA125, and ROMA index had better performance in the diagnosis of postmenopausal ovarian cancer than that of premenopausal ovarian cancer. The overall performance of ROMA and HE4 was better than that of CA125, but it was affected by pathologic types. Conclusions Serum HE4, serum CA125, and ROMA can be used to predict ovarian cancer. HE4 and ROMA have better performance than CA125 in most cases, but pathologic types can also affect them.

Laryngeal metastases from breast cancer: A rare clinical entity Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Ritesh Kumar, Sumit Kumar, Ajay Gogia, Aanchal Kakkar, Sandeep R Mathur Breast cancer is the most common malignancy in females. The common site for metastases is bone, lungs, liver, and regional lymph nodes. Larynx as a metastatic site from breast cancer is extremely rare. The authors report a 63-year-old female treated for carcinoma of right breast 5 years back who presented with hoarseness of voice. Clinicoradiological examination revealed a soft tissue lesion in larynx. Pathological evaluation of the laryngeal lesion revealed metastases secondary to breast cancer. The patient received systemic chemotherapy and local radiotherapy. Patients with a history of breast cancer presenting with hoarseness and shortness of breath should not only be evaluated for laryngeal primary but also for metastases. This case is reported in view of rarity of the case with laryngeal metastases from breast cancer masquerading as primary laryngeal disease. To the best of our knowledge, less than 20 cases of laryngeal metastases from breast cancer had been reported in literature till date. Patients with a history of breast cancer presenting with hoarseness and shortness of breath should not only be evaluated for laryngeal primary but also for metastases. Once the diagnosis is confirmed, the treatment of laryngeal metastases is multidisciplinary. Recognizing metastatic disease and prompt early treatment are very important to improve the quality of life.

Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Raman Preet Kaur, Rubal, Raja Paramjeet Singh Banipal, Rajesh Vashistha, Monisha Dhiman, Anjana Munshi Abstract Background and Purpose: Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared. Material and Methods: Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients. Results: Elevated levels of CRP were found among the diseased in comparison with controls (P < 0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)]. Conclusion: Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high.

Are preoperative serum CA15-3 levels different in breast cancer subgroups? Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Murat Araz, Ismail Beypinar, Sinan Kazan, Fatih Inci, Mesut Celiker, Mukremin Uysal Purpose Breast cancer classifies to 4 major subgroups according to immunohistochemistry staining features as Luminal A, Luminal B, human epidermal growth factor receptor 2 overexpression, and Triple Negative. Cancer Antigen15-3 (CA15-3) is used as a tumor marker in breast cancer while its value in early stage and in breast cancer subgroups is still controversial. In this study, we aimed to investigate that whether it is or not differences of the serum preoperative CA15-3 levels in early breast cancer subgroups. Methods We retrospectively investigated medical records of 751 breast cancer patients who admitted to Afyon Kocatepe University Department of Medical Oncology between January 2010 and December 2016. Total 361 patients were included in this study. The cut off value of Ki-67 was used as 20 to distinguish between Luminal A from Luminal B subgroups. Cutoff values of CA15-3 were evaluated as 25U/mL. Results CA15-3 levels were not significantly different according to clinical features. Molecular subgroups were similar in CA15-3 levels (P = 0.666). Elevated levels of CA15-3 ≥ 25 U/mL were found 34 patients (20.5%) in Luminal A, 15 patients (28.3%) in Luminal B1, 15 patients (20.3%) in Luminal B2, 7 patients (25%) in human epidermal growth factor receptor 2 overexpressed and 9 patients (22.5%) in triple negative groups. Conclusion There was no relationship preoperative CA15-3 levels and breast cancer subgroups.

Everolimus plus endocrine vs endocrine therapy in treatment advanced ER+, HER2− breast cancer patients: A meta-analysis Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Na Wang, Kai Wang, Ya-ting Liu, Fei-xue Song ABSTRACT The purpose of this review was to compare the efficacy and safety of everolimus plus endocrine therapy with endocrine therapy for hormone receptor-positive, human epidermal growth factor 2 negative advanced breast cancer patients. We comprehensively searched the PubMed, the Cochrane Library, EMBASE, Web of Science, Chinese biomedicine literature database, WanFang Data, CNKI, and VIP database for relevant articles. The retrieval time limit is from building the database to July 2018. The computer search was supplemented with a manual search of reference lists for all available review articles. We scanned references of all included studies for additional studies. We included 7 randomized trials involving 1527 patients. Meta-analysis results are as follows: Everolimus plus endocrine therapy group is significantly better than endocrine therapy group in progression-free survival and clinical benefit rate, (hazard ratio [HR] = 0.48, 95% confidence interval [CI 0.42-0.55], P < 0.00001) and (risk ratio = 1.9, 95% CI [1.60-2.26], P < 0.00001). But there was no significant difference between the 2 groups in overall response rate and time to definitive deterioration (risk ratio = 4.37, 95% CI [0.79-24.27], P = 0.21) and (HR = 0.74, 95% CI [0.49-1.11], P = 0.15). In terms of safety, the incidence rate in everolimus plus endocrine therapy was higher than that in endocrine therapy group. Most frequently reported adverse events associated with everolimus treatment were stomatitis, rash, fatigue, diarrhea, decreased appetite, cough, dyspnea, and pneumonitis. The incidences of grade 3-4 adverse events were stomatitis, fatigue, diarrhea, pneumonitis, and hyperglycemia. Everolimus increased the efficacy of endocrine therapy in treatment advanced endocrine receptor-positive, human epidermal growth factor 2 negative breast cancer patients, and the safety profile of the combination is acceptable.

Expressional analysis of MLH1 and MSH2 in breast cancer Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Saima Shakil Malik, Nosheen Masood, Muhammad Asif, Parvez Ahmed, Zafar Ullah Shah, Jahangir Sarwar Khan Abstract Background Mismatch repair proteins are ubiquitous keys in diverse cellular functions and protects the genome by correcting mismatch as post replication error correction machinery. Mismatch repair deficiency was associated with tumor development and progression therefore, current study was aimed to investigate MLH1 and MSH2 expression in breast cancer and correlate patients' clinicopathological factors with status of mismatch repair genes. Material and methods Breast cancer tissues with adjacent normal tissue along with clinical details were collected during surgery from 80 cases. Immunohistochemistry was performed with primary and secondary antibodies for expressional analysis. Results were analyzed using SPSS version 24. Results Immunohistochemical analysis revealed that both MLH1 and MSH2 were crucial in maintaining DNA repair system and loss of these 2 mismatch repair proteins may lead to adverse outcomes in breast cancer. Statistically significant association was found between loss of MLH1 (P = 0.0004; odds ratio 13.8; 95% confidence interval 4.6-41.1), MSH2 (P = 0.0002; odds ratio 14.0; 95% confidence interval 4.7-42.2) and breast cancer. Statistical analysis demonstrated that MLH1 and MSH2 deficiency may lead breast cancer progression to advanced stage, correlated with tumor focality (MLH1 P = 0.001; MSH2 P = 0.002) and chemotherapy (MLH1 P = 0.01; MSH2 P = 0.04). Presence of CK7, GATA 3, and E cadherin tends to increase in mismatch repair deficient breast cancer. Whereas, no association of mismatch repair deficiency was observed with age, tumor grade, positive lymph nodes, menopause, and ER and/or PR status. Conclusion Loss of mismatch repair proteins in breast cancer highlights its potential role in DNA repair mechanisms and helps tumor cells to become resistant against chemotherapeutic drugs. Therefore, mismatch repair deficiency may contribute to breast cancer progression.

Table of Contents Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s):

Oncology

Prevention of cervical cancer: Role of vaccination and screening Priyanka Priyadarshini, Saroj Kumar Das Majumdar, Dillip Kumar Parida Oncology Journal of India 2019 3(1):1-2

Accuracy of magnetic resonance imaging in evaluation of sellar and juxtasellar tumors Pratisruti Hui, Sasmita Parida, Jayashree Mohanty, Mamata Singh, Pradosh Kumar Sarangi Oncology Journal of India 2019 3(1):3-9 Background: Sellar and parasellar/juxtasellar regions are complex areas of the brain, and different varieties of tumors can occur in this area. Preoperative noninvasive diagnosis with magnetic resonance imaging (MRI) is essential for treatment planning. Aim of the Study: The aim of this study is to characterize MRI features of the sellar and juxtasellar tumors and to correlate MRI diagnosis with histopathological diagnosis in order to evaluate the efficiency of MRI. Materials and Methods: Patients with sellar and juxtasellar lesions who were operated during September 2015–August 2017 and the pathological reports were compared with the MRI findings retrospectively. Results: A total of 50 patients were enrolled in the study, and the mean age of presentation was 34.6 years. MRI-based radiological diagnosis showed 21 cases of pituitary macroadenoma, 15 cases of craniopharyngioma, 9 cases of meningioma, 2 cases of germinoma, 1 case of glioma, and 2 cases of epidermoid cysts. Histopathological correlation revealed MRI accuracy of 94.12%, 94%, 100%, 98%, 100%, and 100% for the diagnosis of pituitary macroadenoma, craniopharyngioma, meningioma, germinoma, glioma, and epidermoid cyst, respectively. One case each of pituitary macroadenoma and germinoma diagnosed on MRI comes out to be as craniopharyngioma after final histopathological correlation, whereas one case of craniopharyngioma turned out to be macroadenoma after final histopathological examination. Conclusions: The present study revealed a strong correlation between MRI and histopathological diagnosis for sellar and juxtasellar tumors. MRI is the modality of choice for characterizing sellar and suprasellar lesions.

Congenital mesoblastic nephroma in a premature neonate with initial presentation of hematuria – A case report with review of literature Ipsita Dhal, Goutami Dasnayak, Swati Saxena Oncology Journal of India 2019 3(1):10-12 Congenital mesoblastic nephroma (CMN) is a rare tumor of infancy and consists of 3%–10% of cases among all the pediatric renal tumors. Histologically, it can be classic, cellular, and mixed subtypes, with the cellular variant being difficult to differentiate from Wilms tumors and more aggressive. In this report, macroscopic hematuria was noticed first, and a right renal mass was detected in a 32-week-old premature female neonate, who was born to a 30-year-old woman by emergency cesarean section. Nephrectomy was performed, and histopathological examination of the operated specimen revealed features of cellular variant of CMN.

Squamous cell carcinoma arising from mature cystic teratoma of the ovary Yumkhaibam Sobita Devi, Srigopal Mohanty, Deep Sikha Das, Vimal Sekar Oncology Journal of India 2019 3(1):13-15 Mature cystic teratoma (MCT) is the most common germ cell tumor of the ovary. Malignant transformation is found in only 1%–2% of MCTs, with squamous cell carcinoma (SCC) being the most common type, and is extremely difficult to predict early detection for clinicians. We report a case of MCT with malignant transformation to SCC in a 59-year-old postmenopausal female with the initial complaint of pain in the lower abdomen. The case was suspected as MCT based on the magnetic resonance imaging findings and normal range of serum markers. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was done with intraoperative spillage of the tumor occurred. The patient delayed 2 months for the planned adjuvant chemotherapy followed by completion of surgery in view of suboptimal cytoreduction and intraoperative spillage. She developed recurrent disease as bilateral adnexal deposits. She was on chemotherapy with paclitaxel and carboplatin-based combination regimen, and contrast-enhanced computed tomography scan after three cycles of chemotherapy showed decrease in size of metastatic deposits.

Juvenile trabecular ossifying fibroma of the mandible Samreen Fatma, Surya Narayan Das, Sasmita Singh, Rachna Rath Oncology Journal of India 2019 3(1):16-19 Fibro-osseous lesions are bony lesions where the bone is replaced by fibrous connective tissue and include fibrous dysplasia (FD), cemento-osseous dysplasia, and ossifying fibroma (OF). OF is a benign osteogenic mesenchymal tumor and clinicopathologically divided into juvenile and conventional subtypes. Juvenile OF (JOF) is a rare rapidly growing tumor of the craniofacial bones having aggressive clinical behavior with high recurrence rate. Pathologically, JOF is classified into juvenile trabecular OF (JTOF) and juvenile psammomatoid OF. JTOF microscopically shows proliferation of fibrocellular connective tissue stroma along with immature and woven bony trabeculae with varied histologic features. We report a case of JTOF of the mandible in a 12-year-old male with the initial presentation of painless swelling on the right side lower jaw. Clinicoradiologically, the case was suspected as central giant cell granuloma and odontogenic tumors. He was successfully treated with wide local excision and reconstruction and was on follow-up for 8 months without any recurrence of the disease.

Osteosarcoma presenting with massive malignant pleural effusion Renu Sukumaran, Nileena Nayak, Rari P Mony, Jasmine Kaur, Sreejith G Nair Oncology Journal of India 2019 3(1):20-23 Osteosarcoma is an aggressive primary bone tumor arising from primitive bone-forming cells. The most frequent site of metastasis is the lung followed by bone. However, osteosarcoma presenting as malignant pleural effusion during the initial presentation is extremely rare. Involvement of more than one bone at the time of initial presentation is rare and it is confusing whether these multiple lesions represent multiple primaries or metastasis. We report the case of a 17-year-old male who presented with fever and breathlessness of 1-month duration. Examination revealed massive pleural effusion. Pleural fluid cytology showed malignant cells. On examination, a scalp swelling was also noted. Radiological evaluation revealed multiple bony lesions involving the skull, femur, humerus, and vertebrae. Biopsy of the lesion in the humerus confirmed the diagnosis of osteosarcoma.

Anxiety Disorders

Self- and other-perceptions of interpersonal problems: Effects of generalized anxiety, social anxiety, and depression Publication date: June 2019 Source: Journal of Anxiety Disorders, Volume 65 Author(s): Ki Eun Shin, Michelle G. Newman Abstract Despite attention on overlap and distinction between generalized anxiety disorder (GAD), social anxiety disorder (SAD), and major depressive disorder (MDD), interpersonal specificity (distinct, prototypical interpersonal features) between the disorders has been understudied. There is emerging evidence for such specificity (e.g., Erickson et al., 2016), but most studies relied on self-report, and not all studies controlled for shared variance between the disorders, complicating interpretation of findings. The present study extended the literature by examining unique interpersonal correlates of GAD, SAD, and MDD symptoms on self- and informant-report, and how self-informant agreement (both mean-level and correlation) in perception of interpersonal affiliation, dominance, and distress varied as a function of the symptoms. 369 college-aged participants (43% with clinical-level symptoms for at least one of the disorders (GAD, SAD, MDD), 57% non-disordered) and up to three of their significant others rated participants' interpersonal problems (interpersonal behaviors that were difficult to engage in or engaged in excessively). We found evidence for exploitable tendencies in GAD, socially avoidant and nonassertive tendencies in SAD, and coldness in MDD based on self-report, but not on informant-report. Although self-other correlation was positive across outcomes, participants endorsed higher affiliation and interpersonal distress and lower dominance relative to informants. GAD, SAD, and MDD symptoms showed distinct moderating effects on these self-informant discrepancies. GAD symptoms predicted over-endorsing affiliation, SAD predicted under-endorsing dominance and affiliation, and MDD predicted no discrepancies in affiliation and dominance. The results speak to potential differentiation of the disorders based on distinct patterns of self-other discrepancy in interpersonal perceptions.

Heart rate variability in patients with agoraphobia with or without panic disorder remains stable during CBT but increases following in-vivo exposure Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Jennifer Lara Maria Mumm, Lena Pyrkosch, Jens Plag, Patrick Nagel, Moritz Bruno Petzold, Sophie Bischoff, Lydia Fehm, Thomas Fydrich, Andreas Ströhle Abstract Patients with anxiety disorders have a lower heart rate variability (HRV) than healthy controls. Low HRV is associated with cardiovascular disease and dysfunction of the autonomic nervous system (ANS). The aim of the present study was to investigate if HRV in patients with agoraphobia with or without panic disorder can be influenced by cognitive behavioral therapy (CBT). 73 patients with agoraphobia with or without panic disorder were included in the study. Heart rate (HR) and HRV were recorded at rest before and after CBT and during in-vivo exposure. No changes in HR and HRV were observed throughout therapy. During in-vivo exposure HRV increased significantly and HR exhibited a tendency to decrease. Despite clinical improvement of anxiety symptoms, ANS activity at rest did not seem to be influenced by CBT. However, during in-vivo exposure, HRV changed significantly, indicating a higher parasympathetic activity at the end of exposure.

Do men and women arrive, stay, and respond differently to cognitive behavior group therapy for social anxiety disorder? Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Maya Asher, Haggai Hermesh, Shay Gur, Sofi Marom, Idan Aderka

Measuring treatment outcome in patients with anxiety disorders: A comparison of the responsiveness of generic and disorder-specific instruments Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): S.J. Schawo, I.V.E. Carlier, A.M. van Hemert, E. de Beurs Abstract Background For routine outcome monitoring, generic (i.e., broad-based) and disorder-specific instruments are used to monitor patient progress. While disorder-specific instruments may be more sensitive to therapeutic change, generic measures can be applied more broadly and allow for an assessment of therapeutic change, irrespective of a specific anxiety disorder. Our goal was to investigate whether disorder-specific instruments for anxiety disorders are a valuable (or even necessary) addition to generic instruments for an appropriate assessment of treatment outcome in groups of patients. Methods Data were collected from 2002 to 2013 from psychiatric outpatients in treatment for Social Phobia (SP; n = 834), Generalized Anxiety Disorder (GAD; n = 661), Panic Disorder (PD; n = 944), Obsessive-Compulsive Disorder (OCD; n = 460), and Posttraumatic Stress Disorder (PTSD; n = 691). Instruments used were the generic Brief Symptom Inventory (BSI), The Mood and Anxiety Symptoms Questionnaire (MASQ), and several disorder-specific instruments (e.g., Social Interaction Anxiety Scale, Social Phobia Scale, Panic Appraisal Inventory, etc.). Responsiveness (i.e., sensitivity to therapeutic change) was examined through correlational analyses, effect sizes (ES), and analysis of variance for repeated measures. Results The MASQ appeared generally more responsive than the BSI, except for the BSI Anxiety subscale for PD. Disorder-specific measures equaled the MASQ and BSI in responsiveness. When statistically significant differences occurred, the ES was small. Discussion/conclusions For most anxiety disorder groups (i.e., SP, PD and OCD), the MASQ or BSI was equally suited as disorder-specific instruments to detect change at group level. Exceptions are GAD and PTSD. These findings suggest limited incremental information value of disorder-specific instruments over the MASQ and BSI for measuring change.

A randomized controlled trial of prolonged exposure therapy versus relaxation training for older veterans with military-related PTSD Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Steven R. Thorp, Lisa H. Glassman, Stephanie Y. Wells, Kristen H. Walter, Heather Gebhardt, Elizabeth Twamley, Shahrokh Golshan, James Pittman, Kendra Penski, Carolyn Allard, Leslie A. Morland, Julie Wetherell Abstract Objective Although prolonged exposure (PE) has strong support for treating posttraumatic stress disorder (PTSD), there is little research on PE for older adults. Likewise, Relaxation Training (RT) has shown some benefit for PTSD, but has not been adequately tested in this population. Method This study represents the first randomized controlled trial of two active psychotherapies for PTSD among older adults. Male combat veterans (N = 87; mean age = 65 years) were randomly assigned to 12 sessions of PE (n= 41) or RT (n = 46). Clinician-administered and self-report assessments were conducted at pre-treatment, post-treatment, and six-month follow-up; self-reported symptoms were also measured at each treatment session. Results Multi-level modeling indicated that Clinician-Administered PTSD Scale scores significantly decreased from pre-treatment to follow-up, but the time by treatment condition interaction was not significant. Pre- to post-treatment change was large in PE and moderate in RT, but many gains were lost at follow-up. For self-reported PTSD symptoms, a significant time by treatment condition interaction emerged, suggesting that participants who received PE had both greater decreases in symptoms and a greater rebound in self-reported PTSD symptoms than those who received RT. Unlike PTSD symptoms, depression symptoms neither changed nor were moderated by treatment condition from pre-treatment to follow-up. For self-reported PTSD and depression symptoms assessed at each session, time significantly predicted symptom reductions across psychotherapy sessions. Conclusions PE and RT are well-tolerated, feasible, and effective for older adults, though treatment gains were not maintained at follow-up. Trial registration clinicaltrials.gov Identifier: NCT00539279.

External validation of the International Risk Prediction Algorithm for the onset of generalized anxiety and/or panic syndromes (The Predict A) in the US general population Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Yeshambel T. Nigatu, JianLi Wang Abstract Introduction Multivariable risk prediction algorithms are useful for making clinical decisions and health planning. While prediction algorithms for new onset of anxiety disorders in Europe and elsewhere have been developed, the performance of these algorithms in the Americas is not known. The objective of this study was to validate the PredictA algorithm for new onset of anxiety and/or panic disorders in the US general population. Methods Longitudinal study design was conducted with approximate 2-year follow-up data from a total of 24 626 individuals who participated in Wave 1 and 2 of the US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and who did not have generalized anxiety disorder (GAD) and panic disorder in the past year at Wave 1. The PredictA algorithm was directly applied to the selected participants. Results Among the participants, 5.4% developed GAD and/or panic disorder over two years. The PredictA algorithm had a discriminative power (C-statistics = 0.62, 95%CI: 0.61; 0.64), but poor calibration (p < 0.001) with the NESARC data. The observed and the mean predicted risk of GAD and/or panic disorders in the NESARC were 5.3% and 3.6%, respectively. Particularly, the observed and predicted risks of GAD and/or panic disorders in the highest decile of risk score in the NESARC participants were 13.3% and 10.4%, respectively. Conclusion The PredictA algorithm has acceptable discrimination, but the calibration with the NESARC data was poor. The PredictA algorithm is likely to underestimate the risk of GAD/panic disorders in the US population. Therefore, the use of PredictA in the US general population for predicting individual risk of GAD and/or panic disorders is not encouraged.

Enhanced cognitive control over task-irrelevant emotional distractors in generalized anxiety disorder versus obsessive-compulsive disorder Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Lauren S. Hallion, David F. Tolin, Gretchen J. Diefenbach Abstract Generalized anxiety disorder (GAD) is defined in part by excessive and uncontrollable worry. However, little is known about cognitive control abilities in adults with GAD. The present study examined cognitive control over negative and neutral material in a mixed clinical sample of adults with GAD and/or obsessive-compulsive disorder and a comparison healthy control sample. Participants completed a novel emotional variant of the AX-CPT (eAX-CPT) to index proactive and reactive cognitive control in the presence of negative and neutral distractor stimuli. Participants with GAD demonstrated enhanced cognitive control specifically over negative emotional distractors, relative to neutral distractors (within-subjects) and relative to OCD and controls (between-subjects). Findings were specific to GAD versus trait worry; however, higher trait worry predicted better cognitive control in GAD only. These findings are inconsistent with deficit-based cognitive models of GAD and may be better accounted for by models that conceptualize worry as an intentional (albeit maladaptive) cognitive control or emotion regulation strategy that is actively maintained by individuals with GAD in order to avoid engaging with more distressing emotional information.

Safety behaviors, experiential avoidance, and anxiety: A path analysis approach Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Alex Kirk, Johanna M. Meyer, Mark A. Whisman, Brett J. Deacon, Joanna J. Arch Abstract Avoidance has long been viewed as an etiological mechanism of anxiety disorders. Of more recent focus within this literature is the distinction between avoidance that is trait-based (experiential avoidance) versus contextual (safety behaviors). Whereas both experiential avoidance and safety behaviors have been studied within anxiety research, no known studies have evaluated the direct and indirect relationships of these forms of avoidance in predicting critical outcomes, particularly in conjunction with symptom severity. To address this gap, the current study assessed social anxiety and panic symptoms, experiential avoidance, use of preventive and restorative safety behaviors, and quality of life to determine the direct and indirect contributions of trait-based and contextual avoidance in predicting clinically relevant outcomes via path analysis. U.S. adults with elevated social anxiety or panic symptoms (n = 254) were recruited online. Results from path analysis showed that, across groups, the relationship between symptoms and quality of life was indirectly accounted for by use of preventive safety behaviors. Further, for participants with panic symptoms (but not for those with social anxiety symptoms), experiential avoidance predicted quality of life even after accounting for use of preventive safety behaviors. The results of this study indicate that trait-based and contextual avoidance contribute significantly to clinically relevant outcomes.

Fear extinction learning as a predictor of response to cognitive behavioral therapy for pediatric obsessive compulsive disorder Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Daniel A. Geller, Joseph F. McGuire, Scott P. Orr, Brent J. Small, Tanya K. Murphy, Kathleen Trainor, Rachel Porth, Sabine Wilhelm, Eric A. Storch Abstract Background While cognitive behavior therapy (CBT) is an effective treatment for many children and adolescents with Obsessive Compulsive Disorder (OCD), therapeutic response is variable. Fear conditioning and extinction are central constructs underlying exposure-based CBT. Fear extinction learning assessed prior to CBT may be a useful predictor of CBT response for guiding treatment decisions. Methods Sixty-four youth who participated in a randomized placebo-controlled trial of CBT with and without d-cycloserine (DCS) completed a fear conditioning task. Skin conductance response (SCR) scores were used to measure fear acquisition and extinction to determine whether extinction learning could predict CBT response. Results CBT responders and non-responders appeared to acquire conditioned fear SCRs in a similar manner. However, differences between treatment responders and non-responders emerged during the extinction phase. A responder (responder, non-responder) by conditioned stimulus type (CS+, CS−) interaction showed that CBT responders differentiated the stimulus paired with (CS+) and without (CS−) the unconditioned stimulus correctly during early and late extinction, whereas the CBT non-responders did not (p = .004). Conclusions While the small sample size makes conclusions tentative, this study supports an emerging literature that differential fear extinction may be an important factor underlying clinical correlates of pediatric OCD, including CBT response.

An integrative review of the vigilance-avoidance model in pediatric anxiety disorders: Are we looking in the wrong place? Publication date: May 2019 Source: Journal of Anxiety Disorders, Volume 64 Author(s): Dana Rosen, Rebecca B. Price, Jennifer S. Silk Abstract Enduring cognitive models of anxiety posit that negative biases in information processing are implicated in the etiology, maintenance, and recurrence of anxiety disorders in youth and adults. Specifically, the vigilance-avoidance model of attention is an influential hypothesis proposed to explain anxious individuals' attentional patterns. The vigilance-avoidance model posits that anxious individuals, relative to nonanxious individuals, initially orient more quickly to threatening stimuli and then later avoid threatening stimuli. However, a large body of empirical research examining attentional mechanisms in anxious individuals uses paradigms that do not allow the measurement of the time course of attention. Furthermore, existing reviews that examine the time course of attention only include studies with adults. We systematically review in depth the literature that compares anxious and non-anxious children that takes advantage of research designs that allow the examination of the time course of attention. Across studies, there is not robust support for the vigilance-avoidance model in samples of anxious youth. Future research examining attention biases across time should employ tasks that more directly measure multiple stages of attention, in order to assess if vigilance-avoidance patterns emerge based on sample characteristics or task variables, and to inform intervention efforts.

Strahlentherapie und Onkologie

Wirksamkeit und Sicherheit einer Kohlenstoffionentherapie lokal rezidivierter Rektumkarzinome: Ergebnisse der J‑CROS-Studie 1404 Rektum

Einfluss der prophylaktischen Ganzhirnbestrahlung auf das Gesamtüberleben von Patienten mit einem fortgeschrittenen nicht-kleinzelligen Bronchialkarzinom

Beim HPV-assoziierten Oropharynxkarzinom ist die Radiochemotherapie mit Cisplatin der Bioradiotherapie mit Cetuximab in Bezug auf das Gesamtüberleben überlegen

Endokrine Funktionsstörungen nach Bestrahlung von Hirntumoren bei Kindern und jungen Erwachsenen

Patient- versus physician-reported outcomes in prostate cancer patients receiving hypofractionated radiotherapy within a randomized controlled trial Abstract Purpose The risk of developing acute radiotherapy(RT)-induced side effects may increase with hypofractionated RT. To detect treatment-related side effects, patient-reported outcomes (PROs) might be more reliable than physician-reported outcomes. Therefore, we tried to evaluate the rate of agreement between urinary and gastrointestinal (GI) side effects and the prevalence of side effects reported by patients and by physicians. Methods Data from a randomized controlled trial (RCT) comparing two hypofractionated RT schedules were used. Urinary (nocturia, incontinence, frequency, dysuria, and urgency) and GI (obstruction, diarrhea, vomiting, nausea, bloating, hemorragia, and incontinence) symptoms measured by the EORTC QLQ-C30 and PR-25 were used for PROs. The same symptoms were scored by the physician using the Common Terminology Criteria Adverse Events v4.0. Outcomes were reported at baseline, end of treatment, month 1, and month 3. PROs and physician-reported outcomes were converted in two categories (0 = no symptoms; 1 = symptoms of any severity) and were correlated using the kappa (κ) correlation statistics. Values below 0.40 were considered low agreement. In addition, the prevalence of symptoms was calculated. Results Data from 160 patients were used. The mean value for Cohen's κ was 0.31 (ranging between 0.04 and 0.55) and 0.23 (ranging between 0.04 and 0.47) for urinary and GI symptoms, respectively. Except for three symptoms at baseline, all symptoms reported by patients were higher than those reported by physicians. Conclusion There is low agreement between symptoms reported by patients and physicians, with high rates of underreporting by the physician.

Dosimetric and volumetric effects in clinical target volume and organs at risk during postprostatectomy radiotherapy Abstract Purpose To assess the reproducibility of the dose–volume distribution of the initial simulation CT, generated using volumetric modulated arc therapy (VMAT) planning, during the radiotherapy of the prostatic bed based on weekly cone beam CTs (CBCT). Methods Twenty-three patients, after radical prostatectomy were treated with adjuvant or salvage radiotherapy between July and December 2016 and considered for this evaluation. Weekly CBCT scans (n = 138) were imported into the treatment planning system, and the clinical tumor volume (CTV), the rectum and the bladder were contoured. The initially calculated dose distribution and the dose–volume histograms generated from weekly CBCTs were compared. The prostatic fossa dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 50, 60 and 65 Gy during the treatment were compared to the initial plan, with statistical significance determined using the one-sample t‑test. Results Marked variations in the total organ volume of the rectum and the bladder were observed. The correlation between rectum volume and V50 was not significant (p = 0.487), while the bladder volume and V50 demonstrated a significant correlation. There was no correlation between urinary bladder volume and CTV. The change in rectal volume correlated significantly with CTV. The dose coverage (D98% and D95%) to the prostatic bed could be achieved for all patients due to the ventral shift in the volume differences of the rectum. Conclusion Weekly CBCTs can be considered as adequate verification tools to assess the interfractional variability of the CTV and organs at risk. The proven volume changes in the urinary bladder and the rectum do not compromise the final delivered dose in the CTV.

A fatal case of Fournier's gangrene during neoadjuvant radiotherapy for rectal cancer Abstract Purpose To report the development of an ultimately fatal occurrence of Fournier's gangrene in a rectal cancer patient undergoing neoadjuvant radiotherapy without chemotherapy. Methods A 53-year-old male patient with G2 cT3 cN1a cM0 stage IIIB adenocarcinoma of the lower rectum and several comorbidities including ulcerative colitis was treated with 56 Gy to the primary tumor in 28 fractions because he declined the recommended simultaneous chemotherapy. He was also enrolled in the ketogenic diet arm of our KETOCOMP study, so that prospective measurements of blood parameters, quality of life, and body composition were made. Results The patient died 6 days after completion of radiotherapy due to septic shock associated with Fournier's gangrene reaching from the right buttock into the gluteal muscles and descending into the scrotum. In retrospect, there were several signs probably indicating the development of the gangrene: (i) a decline in bioelectrical phase angle; (ii) an accelerated weight and fat-free mass loss starting in the third week of radiotherapy; (iii) an increase in C-reactive protein (CRP) and concurrent drop in high-density lipoprotein (HDL) cholesterol and insulin-like growth factor(IGF)-1 concentrations; and (iv) the occurrence of a sharp pain in the perianal region reported in the fifth week of radiotherapy. Notably, his self-reported quality of life score was the same at the end of as before radiotherapy. Conclusions This case highlights the occurrence of Fournier's gangrene as an extremely rare but life-threatening complication during neoadjuvant radiotherapy for rectal cancer which should be refreshed in the awareness of radiation oncologists and radiologists.

Comparison of 68  Ga-PSMA ligand PET/CT versus conventional cross-sectional imaging for target volume delineation for metastasis-directed radiotherapy for metachronous lymph node metastases from prostate cancer Abstract Purpose To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in a comparative retrospective contouring study. Patients and methods Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a) based on conventional imaging (CT/MRI) and (b) based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared. Results With the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9–565.2] versus 44.9 ml [range 4.9–481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRI × 100) were 45.7% (range 0–96.9) for the GTV and 71.7% (range 9.8–98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003). Conclusion 68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.

Impact of androgen deprivation therapy on apparent diffusion coefficient and T2w MRI for histogram and texture analysis with respect to focal radiotherapy of prostate cancer Abstract Purpose Accurate prostate cancer (PCa) detection is essential for planning focal external beam radiotherapy (EBRT). While biparametric MRI (bpMRI) including T2-weighted (T2w) and diffusion-weighted images (DWI) is an accurate tool to localize PCa, its value is less clear in the case of additional androgen deprivation therapy (ADT). The aim of this study was to investigate the value of a textural feature (TF) approach on bpMRI analysis in prostate cancer patients with and without neoadjuvant ADT with respect to future dose-painting applications. Methods 28 PCa patients (54–80 years) with (n = 14) and without (n = 14) ADT who underwent bpMRI with T2w and DWI were analyzed retrospectively. Lesions, central gland (CG), and peripheral zone (PZ) were delineated by an experienced urogenital radiologist based on localized pre-therapeutic histopathology. Histogram parameters and 20 Haralick TF were calculated. Regional differences (i. e., tumor vs. PZ, tumor vs. CG) were analyzed for all imaging parameters. Receiver-operating characteristic (ROC) analysis was performed to measure diagnostic performance to distinguish PCa from benign prostate tissue and to identify the features with best discriminative power in both patient groups. Results The obtained sensitivities were equivalent or superior when utilizing the TF in the no-ADT group, while specificity was higher for the histogram parameters. However, in the ADT group, TF outperformed the conventional histogram parameters in both specificity and sensitivity. Rule-in and rule-out criteria for ADT patients could exclusively be defined with the aid of TF. Conclusions The TF approach has the potential for quantitative image-assisted boost volume delineation in PCa patients even if they are undergoing neoadjuvant ADT.

Chemoradiotherapy for anal cancer: are we as good as we think? Abstract Definitive chemoradiotherapy (CRT) is the standard treatment for anal squamous cell carcinoma (ASCC). Data regarding treatment outcome according to TNM classification is scarce. Here, we review data of randomized trials and retrospective cohorts suggesting a poor 3‑year disease-free survival (DFS; or progression-free survival, PFS) of approximately 60%, or even lower, in patients with locally advanced T3–4 and/or N+ disease, while patients with T1–2N0 ASCC have 3‑year DFS/PFS rates exceeding 80%. These results are in line with our data in a cohort of 210 patients with ASCC treated with definitive 5‑fluorouracil/mitomycin C‑based CRT to a total dose of 50.4 Gy plus a boost of 3.6–10.8 Gy. The implications of these findings and the current trials testing radiotherapy dose escalation/de-escalation strategies are reported. Finally, we will discuss the strong rationale for testing immune checkpoint blockade (ICB) with CRT in clinical trials to improve results, especially in patients with advanced ASCC.

無爲

When your body is not aligned [形不正],

The inner power will not come. 

When you are not tranquil within [中不靜], 

Your mind will not be well ordered. 

Align your body, assist the inner power [正形攝德], 

Then it will gradually come on its own.

When you enlarge your mind and let go of it,

When you relax your [qi 氣] vital breath and expand it, 

When your body is calm and unmoving: 

And you can maintain the One and discard the myriad disturbances. 

You will see profit and not be enticed by it, 

You will see harm and not be frightened by it. 

Relaxed and unwound, yet acutely sensitive, 

In solitude you delight in your own person. 

This is called "revolving the vital breath": 

Your thoughts and deeds seem heavenly.

There is a numinous [mind] naturally residing within [有神自在身];

One moment it goes, the next it comes, 

And no one is able to conceive of it. 

If you lose it you are inevitably disordered; 

If you attain it you are inevitably well ordered. 

Diligently clean out its lodging place [敬除其舍] 

And its vital essence will naturally arrive [精將自來]. 

Still your attempts to imagine and conceive of it. 

Relax your efforts to reflect on and control it. 

Be reverent and diligent 

And its vital essence will naturally stabilize. 

Grasp it and don't let go 

Then the eyes and ears won't overflow 

And the mind will have nothing else to seek. 

When a properly aligned mind resides within you [正心在中], 

The myriad things will be seen in their proper perspective.