Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component related to a more malignant behavior?

BACKGROUND/AIMS: Acinar cell carcinomas are uncommon malignant tumors of the pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some authors have estimated acinar cell tumors to be as aggressive as ductal adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to have a favorable clinical outcome. This discrepancy in prognosis may be related to the cellular components of the tumor. METHODOLOGY: With the aim to evaluate the possible relationship between the presence of neuroendocrine differentiation and behavior of these tumors, the authors reviewed all patients presenting acinar cell carcinoma of the pancreas in the last 5 years with emphasis in the immunohistochemical evaluation. RESULTS: Four patients presented neuroendocrine differentiation on immunohistochemical evaluation and had a more benign outcome. Two patients without neuroendocrine component had a disseminated disease at presentation. This data suggests that this tumor is less aggressive than ductal adenocarcinoma and even with nodal involvement, long-term survival after complete resection can be achieved. CONCLUSIONS: It is possible that the absence of neuroendocrine component may be related to a less favorable outcome and adjuvant therapy may be necessary. Due to the rarity of this pancreatic tumor, this relationship remains to be confirmed with a multicentric study including a larger number of patients.     

Clonal origin of non-medullary thyroid tumours assessed by non-random X-chromosome inactivation.

OBJECTIVE: X-chromosome inactivation analysis was performed in order to assess the clonal origin of non-medullary thyroid tumours and to distinguish between multicentricity and multifocality in multiple papillary thyroid carcinoma (PTC). METHODS: One hundred and thirteen tumour samples from 31 patients with isolated PTC, 16 patients with multinodular PTC, 14 patients with follicular thyroid adenoma (FTA) and 15 patients with follicular thyroid carcinoma (FTC) were collected. The corresponding normal thyroid tissues were analysed, and in 14 cases, tumour-surrounding tissue was also studied. Genomic DNA was digested with HpaII and HhaI previous to PCR amplification of the polymorphic CAG repeat, on exon 1 of the human androgen receptor gene (HUMARA). PCR products were analysed by denaturing gel electrophoresis, silver staining and densitometric analysis. PCR products were also used to determine the number of CAG repeats of patients with isolated PTC, FTA, FTC and of 41 healthy volunteers. RESULTS: Heterozygosity for the HUMARA polymorphism was found in 64/76 (84%) cases. Lyonization of the thyroid was observed in 15/76 (20%) cases, which were excluded from clonal analysis. Except for two cases of isolated PTC, all tumour samples studied presented monoclonal X-inactivation patterns, while normal thyroid tissue was polyclonal. Monoclonal patterns were also found in 4/14 tumour-surrounding tissues. No difference was found in the length of CAG alleles between patients and controls. Of eight informative cases of multinodular PTC, three showed evidence of multicentricity and five revealed patterns consistent with multifocality. CONCLUSIONS: Both isolated and multinodular PTC as well as FTA and FTC are of monoclonal origin. Our results also suggest that approximately one-third of multiple PTC have an independent origin for the different nodules (multicentricity). Monoclonality was also found in tissues surrounding some PTC nodules. No association was found between the length of CAG alleles and thyroid malignancies.     

Development and Validation of the Athlete Fear Avoidance Questionnaire

Context

The fear-avoidance model was developed in an attempt to explain the process by which “pain experience” and “pain behavior” become dissociated from the actual pain sensation in individuals who manifest the phenomenon of exaggerated pain perception. High levels of fear avoidance can lead to chronic pain and disability and have successfully predicted rehabilitation time in the work-related–injury population. Existing fear-avoidance questionnaires have all been developed for the general population, but these questionnaires may not be specific enough to fully assess fear avoidance in an athletic population that copes with pain differently than the general population.

Objective

To develop and validate the Athlete Fear Avoidance Questionnaire (AFAQ).

Design

Qualitative research to develop the AFAQ and a cross-sectional study to validate the scale.

Patients or Other Participants

For questionnaire development, a total of 8 experts in the fields of athletic therapy, sport psychology, and fear avoidance were called upon to generate and rate items for the AFAQ. For determining concurrent validity, 99 varsity athletes from various sports participated.

Data Collection and Analysis

A total of 99 varsity athletes completed the AFAQ, the Fear-Avoidance Beliefs Questionnaire, and the Pain Catastrophizing Scale. We used Pearson correlations to establish concurrent validity.

Results

Concurrent validity was established with significant correlations between the AFAQ and the Fear Avoidance Beliefs Questionnaire-Physical Activity (r = 0.352, P > .001) as well as with the Pain Catastrophizing Scale (r = 0.587, P > .001). High internal consistency of our questionnaire was established with a Cronbach α coefficient of 0.805. The final version of the questionnaire includes 10 items with good internal validity (P < .05).

Conclusions

We developed a questionnaire with good internal and external validity. The AFAQ is a scale that measures sport-injury–related fear avoidance in athletes and could be used to identify potential psychological barriers to rehabilitation.Key Words: fear-avoidance model, scale, sports, athletic injuries, rehabilitation, psychology

Key Points

• We developed and validated the Athlete Fear Avoidance Questionnaire to assess pain-related fear in athletes.
• Pain-related fear or fear avoidance plays a critical role in the rehabilitation of patients with low back pain and work-related injuries. High levels of fear avoidance in athletes may affect rehabilitation times.

Most health professionals who work with injured athletes have encountered situations in which an athlete was struggling psychologically to return to play or the duration of rehabilitation was disproportionate to the athlete''s initial physical dysfunction. To date, a few scales measure athletes'' readiness to return to play, such as the Sports Inventory for Pain and the Injury–Psychological Readiness to Return to Sport Scale.^1,2 The Sports Inventory for Pain was developed specifically to identify beneficial and detrimental pain-coping strategies among the athletic population, but the authors worked with a student population to generate the items on the questionnaire, rather than a panel of experts in the field, and they did not establish concurrent validity. The Injury–Psychological Readiness to Return to Sport Scale was developed as a tool to assess an athlete''s confidence and psychological readiness to go back to play; however, it was designed to be administered at the end of an athlete''s rehabilitation process and, therefore, cannot be used to address psychological barriers at the beginning of rehabilitation that may lengthen the time to return to play.² Neither scale has been used extensively, but the fear-avoidance model (FAM), a psychological model well established in the general population, has been used extensively for its predictive value. For example, Sullivan et al³ noted that the Pain Catastrophizing Scale (PCS) has been cited more than 900 times on Web of Science since 1995.The FAM is based on the emotional reaction of pain perception and high levels of fear avoidance that can lead to dysfunction.⁴ The FAM was created in an attempt to explain the development of chronic pain from acute pain. The model comprises 4 components: fear of pain, kinesiophobia, fear-avoidance belief, and catastrophizing. According to the FAM, exaggerated pain perception could lead to the development of chronic pain,⁴ and fear of pain is a main focus. There are 2 possible coping reactions to fear of pain: confrontation and avoidance. Individuals who experience elevated levels of fear of pain with signs of fear avoidance in response to acute pain are more likely to develop chronic pain than those who confront their fear of pain.⁴ The FAM assessment tools were all developed for the general population or patients with chronic low back pain. The main questionnaires used to assess the 4 components of the FAM are the Fear of Pain Questionnaire-III, the PCS, the Tampa Scale for Kinesophobia, and the Fear-Avoidance Beliefs Questionnaire (FABQ). The FABQ was developed in part for patients with work-related injuries.⁵ Injured varsity athletes may not relate to work-specific items on the FABQ, such as “My pain was caused by my work or by an accident at work.” Although some of the questionnaires, such as the PCS, have been validated on athletes, they were not developed specifically for the athletic population.⁶ In fact, the FAM questionnaires can be used to predict outcomes.^7,8 Klenerman et al⁷ conducted a study to determine whether chronic pain could be predicted from acute low back pain in the general population. Results indicated that patients with acute low back pain either will improve within 2 months or will develop chronic pain and that the FAM appears to be the best predictor of the course of low back pain within the first 2 months.⁷ In another study, Fritz and George⁸ aimed to identify psychosocial factors that could predict return to work in patients with acute work-related back pain. The results revealed that the FABQ-Work (FABQ-W) was the strongest predictor of work status and may be used to predict return to work in patients with acute work-related low back pain.⁸ The authors of the PCS also established that people who catastrophize have higher levels of pain and disability than people who do not.⁹Some studies have indicated that parts of the FAM can influence athletes'' rehabilitation.^6,10,11 Kvist et al¹⁰ also reported on the psychological effect an injury can have on a player. Of the 47% who did not return to their sport, 24% did not return to play because of their fear of reinjury.¹⁰ People who returned to their preinjury levels of activity had the lowest levels of fear of reinjury, whereas people who did not return to their preinjury levels of activity had a higher fear of reinjury.¹⁰ The results of these studies might have been stronger using a scale that was developed specifically for athletes. To date, no questionnaire or scale has been specifically developed to assess fear avoidance or pain-related fear in athletes, who differ from the general population in their mentality and reality (ie, the role of sports or activity in their lives). Furthermore, athletes are exposed to pain and sports injuries relatively often, so knowing whether fear avoidance is a major concern among that population is important. Therefore, taking fear avoidance into account might be useful to establish the most appropriate and effective rehabilitation plan and, consequently, to reduce the time for return to play. A questionnaire specific to athletes might help establish how the FAM or pain-related fear can influence the athletic population, specifically regarding rehabilitation.Therefore, the aims of our study were to develop and validate the Athlete Fear Avoidance Questionnaire (AFAQ). We used a qualitative study design, a modified Delphi technique, to develop the scale and then a cross-sectional study to establish its validity.     

Correction: Synthetic routes for a variety of halogenated (chiral) acetic acids from diethyl malonate

Correction for ‘Synthetic routes for a variety of halogenated (chiral) acetic acids from diethyl malonate’ by Manuel R. Mazenauer et al., RSC Adv., 2017, 7, 55434–55440.

An incorrect email address was provided for affiliation a, the correct version, along with capitalisation of Zürich in affiliation b, is shown below.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.