Photodynamic Therapy Effective for the Treatment of Actinic Keratosis and Basal Cell Carcinoma in Bullous Pemphigoid Patients

Publication date: Available online 1 April 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Theresa N. Canavan, Salma Faghri de la Feld, Conway Huang, Naveed Sami
Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.



http://ift.tt/2mZrWIF

Expression and splicing of Ikaros family members in murine and human thymocytes

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Julie L. Mitchell, Amara Seng, Thomas M. Yankee
The Ikaros family of transcription factors includes five highly homologous members that can homodimerize or heterodimerize in any combination. Dimerization is essential for their ability to bind DNA and function as transcription factors. Previous studies showed that eliminating the function of the entire family blocks lymphocyte development while deletion of individual family members has relatively minor defects. These data indicate that multiple family members function during T cell development, so we examined the changes in expression of each family member as thymocytes progressed from the CD4⁻CD8⁻ double negative (DN) to the CD4⁺CD8⁺ double positive (DP) developmental stage. Further, we compared the expression of each family member in murine and human thymocytes. In both species, Ikaros and Aiolos mRNA levels increased as thymocytes progressed through the DN to DP transition, but the corresponding increases in protein levels were only observed in mice. Further, Ikaros and Aiolos underwent extensive alternative splicing in mice, whereas only Ikaros was extensively spliced in humans. Helios mRNA and protein levels decreased during murine T cell development, but increased during human T cell development. These differences in the expression and splicing of Ikaros family members between human and murine thymocytes strongly suggest that the Ikaros family of transcription factors regulates murine and human T cell development differently, although the similarities across Ikaros family members may allow different proteins to fulfill similar functions.



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Corrigendum to “MiR-146a modulates macrophage polarization in systemic juvenile idiopathic arthritis by targeting INHBA” [Mol. Immunol. 77 (2016) 205–212]

Publication date: Available online 31 March 2017
Source:Molecular Immunology
Author(s): Dan Li, Mingyue Duan, Yuan Feng, Lingling Geng, Xiaoqing Li, Wanggang Zhang




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Impact of adjuvant chemotherapy on survival of women with T1N0M0, hormone receptor negative breast cancer

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Nanthini Thevi Bhoo-Pathy, Shinako Inaida, Shiro Tanaka, Nur Aishah Taib, Cheng-Har Yip, Marniza Saad, Koji Kawakami, Nirmala Bhoo-Pathy
BackgroundThe benefit of adjuvant chemotherapy in women with T1N0M0 breast cancers is unclear. While gene expression-based prognostic assays may aid management of women with early estrogen receptor (ER) positive tumors, therapeutic decision-making in women with early stage ER negative tumors remains fraught with difficulties. We investigated the association between adjuvant chemotherapy and overall survival in women with T1N0M0, hormone receptor negative breast cancers.MethodAll newly diagnosed breast cancer patients with node-negative and hormone receptor negative tumors measuring≤2cm at the University Malaya Medical Centre (Malaysia) from 1993 to 2013 were included. Mortality of patients with and without adjuvant chemotherapy were compared and adjusted for possible confounders using propensity score.ResultsOf 6732 breast cancer patients, 341 (5.1%) had small (≤2cm), node-negative and hormone receptor negative tumors at diagnosis. Among them, only 214 (62.8%) received adjuvant chemotherapy. Five-year overall survival was 88.1% (95% confidence interval (CI): 82.0%–94.2%) for patients receiving chemotherapy and 89.6% (95% CI: 85.1%–94.1%) for patients without chemotherapy. Chemotherapy was not associated with survival following adjustment for age, ethnicity, tumor size, tumor grade, HER2 status, lympho-vascular invasion, type of surgery and radiotherapy administration. However, chemotherapy was associated with a significant survival advantage (adjusted hazard ratio: 0.35, 95%CI: 0.14–0.91) in a subgroup of women with high-grade tumors.ConclusionAdjuvant chemotherapy does not appear to be associated with a survival benefit in women with T1N0M0, hormone receptor negative breast cancer except in those with high-grade tumors.



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Subjective recollection independent from multifeatural context retrieval following damage to the posterior parietal cortex

Publication date: Available online 1 April 2017
Source:Cortex
Author(s): Elisa Ciaramelli, Giorgia Faggi, Cristina Scarpazza, Flavia Mattioli, Julia Spaniol, Simona Ghetti, Morris Moscovitch
This study investigated whether damage to the posterior parietal cortex (PPC) impairs the capacity to retrieve multiple aspects of the encoding context in which items were studied, or whether it impairs the subjective awareness of recollection. Patients with lesions to the PPC (PPC patients) and healthy controls memorized words along with the position in which the words were presented on the screen and the ink color in which they were printed. We studied PPC patients' recognition and source memory performance, as well as subjective recollection as indexed by Remember/Know judgments. PPC patients had preserved recognition memory, and gave a similar number of R responses as did controls. Moreover, PPC patients' source memory performance, including memory for multiple contextual features, was similar to the controls'. However, whereas healthy controls were more likely to select R responses with correct multifeatural source judgments compared to K responses, PPC patients were not. These findings indicate that the PPC plays a role in the subjective experience and metamnemonic evaluation of memory contents.



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SYSTEMATIC REVIEW AND META-ANALYSIS OF LOCAL RESECTION OR TRANSANAL ENDOSCOPIC MICROSURGY VERSUS RADICAL RESECTION IN STAGE I RECTAL CANCER: A REAL STANDARD?

Publication date: Available online 1 April 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Geneviève Veereman, Joan Vlayen, Jo Robays, Nicolas Fairon, Stordeur Sabine, Christian Rolfo, Didier Bielen, Alain Bols, Pieter Demetter, André D'hoore, Karin Haustermans, Alain Hendlisz, Arnaud Lemmers, Daniel Leonard, Freddy Penninckx, Eric Van Cutsem, Marc Peeters
Current guidelines recommend radical resection for stage I rectal cancer. However, since screening programs are being installed, an increasing number of cancers are being detected in early stages. Endoscopic resection is often performed at the time of diagnosis.This systematic review was undertaken to review the evidence on endoscopic approach vs. radical resection for stage I rectal cancer. Recommendations were issued based on the GRADE methodology and risk stratification used in clinical practice. A systematic search (until March 2015) identified 2 meta-analyses and 1 additional randomized trial. For the primary outcomes (overall survival, disease-free survival, local recurrence-free survival and metastasis-free survival) no evidence could be found on the superiority of local or radical resection. Secondary outcomes (blood loss, hospital stay, operative time, number of permanent stomas and perioperative deaths) were in favour of local resection. The authors strongly recommend radical resection for T2 rectal cancer, but consider 'en bloc' local resection sufficient for pT1sm1 rectal cancers when confirmed pathologically. Discussion by a multidisciplinary team and adequate surveillance remain mandatory.



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Headspace single-drop microextraction coupled with microvolume fluorospectrometry for highly sensitive determination of bromide

Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Adrián García-Figueroa, Francisco Pena-Pereira, Isela Lavilla, Carlos Bendicho
This work reports on the development of a novel methodology for bromide determination by combining headspace single-drop microextraction with microvolume fluorospectrometry. The method lies in the in situ generation of bromine, transfer of the volatile to the headspace and trapping/reaction onto a fluorescein-containing aqueous drop exposed to the gas phase. The decrease in the fluorescence intensity enabled the determination of bromide without dilution of the enriched microdrop. Experimental parameters influencing the performance of the method, namely, fluorescence parameters, extractant phase composition, bromine generation conditions and microextraction time, were evaluated and controlled. Under optimal conditions, an enrichment factor of 243 was attained. The limits of detection and quantification achieved under optimal conditions for bromide were found to be 1.4 and 4.4µgL⁻¹, respectively. The intra-day repeatability, expressed as relative standard deviation, was 4.4% (n=6). Besides, the inter-day reproducibility, performed at four different days, was 7.1%. Finally, the developed method was successfully applied to the determination of bromide in different water samples, showing recovery values in the range of 95–110%, and validated against certified reference material BCR-611 (ground water, Br⁻ low level). The proposed method represents a highly convenient approach for monitoring of bromide at very low concentrations.

Graphical abstract

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Micro-sampling method based on high-resolution continuum source graphite furnace atomic absorption spectrometry for calcium determination in blood and mitochondrial suspensions

Publication date: 1 August 2017
Source:Talanta, Volume 170
Author(s): Beatriz Gómez-Nieto, Mª Jesús Gismera, Mª Teresa Sevilla, Jorgina Satrústegui, Jesús R. Procopio
A micro-sampling and straightforward method based on high resolution continuum source atomic absorption spectrometry (HR-CS AAS) was developed to determine extracellular and intracellular Ca in samples of interest in clinical and biomedical analysis. Solid sampling platforms were used to introduce the micro-samples into the graphite furnace atomizer. The secondary absorption line for Ca, located at 239.856nm, was selected to carry out the measurements. Experimental parameters such as pyrolysis and atomization temperatures and the amount of sample introduced for the measurements were optimized. Calibration was performed using aqueous standards and the approach to measure at the wings of the absorption lines was employed for the expansion of the linear response range. The limit of detection was of 0.02mgL⁻¹ Ca (0.39ng Ca) and the upper limit of linear range was increased up to 8.0mgL⁻¹ Ca (160ng Ca). The proposed method was used to determine Ca in mitochondrial suspensions and whole blood samples with successful results. Adequate recoveries (within 91–107%) were obtained in the tests performed for validation purposes.

Graphical abstract

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Nanocoating cellulose paper based microextraction combined with nanospray mass spectrometry for rapid and facile quantitation of ribonucleosides in human urine

Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Lingzhong Wan, Haijing Zhu, Yafeng Guan, Guangming Huang
A rapid and facile analytical method for quantification of ribonucleosides in human urine was developed by the combination of nanocoating cellulose paper based microextraction and nanoelectrospray ionization-tandem mass spectrometry (nESI-MS/MS). Cellulose paper used for microextraction was modified by nano-precision deposition of uniform ultrathin zirconia gel film using a sol-gel process. Due to the large surface area of the cellulose paper and the strong affinity between zirconia and the cis-diol compounds, the target analytes were selectively extracted from the complex matrix. Thus, the detection sensitivity was greatly improved. Typically, the nanocoating cellulose paper was immersed into the diluted urine for selective extraction of target analytes, then the extracted analytes were subjected to nESI-MS/MS detection. The whole analytical procedure could be completed within 10min. The method was evaluated by the determination of ribonucleosides (adenosine, cytidine, uridine, guanosine) in urine sample. The signal intensities of the ribonuclesides extracted by the nanocoating cellulose paper were greatly enhanced by 136–459-folds compared with the one of the unmodified cellulose paper based microextraction. The limits of detection (LODs) and the limits of quantification (LOQs) of the four ribonucleosides were in the range of 0.0136–1.258μgL⁻¹ and 0.0454–4.194μgL⁻¹, respectively. The recoveries of the target nucleosides from spiked human urine were in the range of 75.64–103.49% with the relative standard deviations (RSDs) less than 9.36%. The results demonstrate the potential of the proposed method for rapid and facile determination of endogenous ribonucleosides in urine sample.

Graphical abstract

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Long-term Quality of Life in Prostate Cancer Patients Treated with Cesium-131

Publication date: Available online 31 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Scott M. Glaser, Katherine S. Chen, Ronald M. Benoit, Ryan P. Smith, Sushil Beriwal
PurposeProstate brachytherapy as monotherapy or in combination with external beam radiation therapy (EBRT) represents a curative treatment option for men with prostate cancer. Of the radioactive isotopes approved for use in prostate brachytherapy, Cesium-131 (Cs-131) is the newest to market and has the shortest half-life. This property may impact resolution of acute voiding toxicities associated with brachytherapy. The aim of this study is to evaluate long-term patient-reported quality of life (QOL) scores in men treated at our institution with Cs-131 prostate brachytherapy.Materials and MethodsPatients treated greater than 4 years ago with Cs-131 (n=290) were asked to fill out an Expanded Prostate Cancer Index Composite (EPIC) QOL questionnaire and American Urological Association Symptom Score (AUASS) survey, before treatment and at each follow-up appointment. We compared patients' EPIC and AUA scores at baseline to scores at a last follow-up of at least 4 years post-treatment using the Wilcoxon signed-rank test.ResultsAt a median last follow-up of 5.5 years post-treatment with Cs-131 prostate brachytherapy, there were no clinically significant changes in the EPIC or AUA scores from baseline. There was statistical worsening in the EPIC urinary incontinence subscore. Subset analyses revealed improved QOL outcomes in patients who received EBRT or alpha-blocker therapy (ABT), while androgen deprivation therapy (ADT) was not associated with differences in QOL change.ConclusionsOur results demonstrate minimal long-term changes in urinary or bowel patient reported quality of life with Cs-131 prostate brachytherapy. These findings suggest that patients treated with this isotope are able to recover and then maintain their baseline quality of life in the long term.

Teaser

We evaluated long-term patient-reported quality of life changes with EPIC and AUA questionnaires in men treated at our institution with Cesium-131 prostate brachytherapy. At a median follow-up of 5.5 years post-treatment, there were not any clinically significant changes in the EPIC Urinary Summary score, EPIC Bowel Summary score, or AUA symptom score from patient baseline scores, indicating excellent long-term tolerability of this treatment modality.


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Radiotherapy in the Middle East: Local and Regional Targets

Publication date: Available online 31 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Benjamin W. Corn, Zvi Symon




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Adjuvant Chemoradiotherapy in Cervical Cancer and the Impact of Timing and Duration on Treatment Outcome

Publication date: Available online 31 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sachin Jhawar, Lara Hathout, Mohamed A. Elshaikh, Sushil Beriwal, William Small, Omar Mahmoud
PurposeWorse Treatment outcomes are expected with prolongation of overall treatment time (OTT) during definitive chemoradiotherapy of cervical cancer. In the adjuvant setting, data on the relative importance of OTT and the importance of radiotherapy and chemotherapy synchronization are scarce. Using the National Cancer Data Base, we aimed to evaluate the impact of these treatment variables on overall survival in the adjuvant chemoradiotherapy setting.MethodsThe analysis included non-metastatic cervical cancer patients undergoing hysterectomy followed by adjuvant chemoradiotherapy. The proportional hazard model estimated the effect of prognostic factors (age, comorbidity, race, tumor size, grade and histology, number of high risk pathologic factors) and time-related variables (surgery to radiotherapy start interval (SR), OTT (radiotherapy start to end dates), package time (from diagnosis date to CRT end date) and optimum chemoradiotherapy synchronization (if chemotherapy and radiation start date coincided) on survival.ResultsOf the 3051 patients, 60% finished RT within 7 weeks and 85% had optimum chemoradiotherapy. Among other factors, univariate analysis identified longer OTT (hazards ratio (HR): 1.33; p<0.001), longer SR (HR: 1.17; p=0.05) and non-optimum CRT timing (HR: 1.21; p=0.04) as poor prognosticators. Of these factors, SR (HR: 1.20; p=0.04) and OTT (HR: 1.21; p=0.002) retained significance on multivariate analysis. OTT exceeding 7 weeks remained a significant factor even after propensity score matching (p=0.04).ConclusionsOur analysis suggests that prolongation of adjuvant chemoradiotherapy duration beyond 7 weeks is associated with poor survival, and surgery to radiotherapy interval less than 8 weeks should be attempted whenever clinically feasible.

Teaser

In the definitive management of cervical cancer, prolongation of the overall treatment time is associated with poor outcome. Similar evidence is lacking in the adjuvant setting. A large population based database was used to assess the prognostic impact of disease-related as well as time-related/treatment variables on survival. Reducing surgery-to-radiation interval below 8 weeks and chemoradiotherapy duration below 7 weeks was associated with improved survival.


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The effect of inspiratory and expiratory loads on abdominal muscle activity during breathing in subjects “at risk” for the development of chronic obstructive pulmonary disease and healthy

Publication date: Available online 31 March 2017
Source:Journal of Electromyography and Kinesiology
Author(s): António Mesquita Montes, Carlos Crasto, Cristina Argel de Melo, Rita Santos, Susana Pereira, João Paulo Vilas-Boas
The abdominal muscle activity has been shown to be variable in subjects with chronic obstructive pulmonary disease (COPD) when respiratory demand increases and their recruitment pattern may change the mechanics, as well as the work and cost of breathing. The scientific evidence in subjects "at risk" for the development of COPD may be important to understand the natural history of this disease. This study aims to evaluate the effect of inspiratory and expiratory loads on the abdominal muscle activity during breathing in subjects "at risk" for the development of COPD and healthy. Thirty-one volunteers, divided in "At Risk" for COPD (n=17; 47.71±5.11 years) and Healthy (n=14; 48.21±6.87 years) groups, breathed at the same rhythm without load and with 10% of the maximal inspiratory or expiratory pressures, in standing. Surface electromyography was performed to assess the activation intensity of rectus abdominis (RA), external oblique and transversus abdominis/internal oblique (TrA/IO) muscles, during inspiration and expiration. During inspiration, in "At Risk" for COPD group, RA muscle activation was higher with loaded expiration (p=0.016); however, in Healthy group it was observed a higher activation of external oblique and TrA/IO muscles (p<0.050). During expiration, while in "At Risk" for COPD group, RA muscle activation was higher with loaded inspiration (p=0.009), in Healthy group TrA/IO muscle showed a higher activation (p=0.025). Subjects "at risk" for the development of COPD seemed to have a specific recruitment of the superficial layer of ventrolateral abdominal wall for the mechanics of breathing.



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In memoriam of Professor Dr. Dr. Gert-Horst Schumacher

Publication date: Available online 1 April 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Thomas Koppe, Jochen Fanghänel




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CpG dinucleotide positioning patterns determine the binding affinity of methyl-binding domain to nucleosomes

Publication date: Available online 1 April 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Agnes Mendonca, Oscar F. Sanchez, Wenjie Liu, Zhe Li, Chongli Yuan
The methyl-binding domain of MBD1 is a common methyl CpG binding motif and has been linked to transcriptional repression. Understanding the dynamics of MBD1 binding to nucleosomal DNA is crucial, but the molecular interactions between MBD1 and chromatin remain elusive. In this study, we found the binding of MBD1 to nucleosomes demonstrates sequence preferences depending on the position of the methyl groups on the nucleosome. Specifically, binding was favored at ^meCpG sites in the dyad proximal region and facing towards the histone octamers. At locations where the ^meCpG sites face away from the histone octamer, the binding affinity was significantly lower. Interestingly, the binding of ΔMBD1 at methylated CpG sites facing away from histone octamers induces conformational changes of nucleosomes, resulting in a more "open" conformation. The biological implication of DNA methylation is thus likely to be synergistically regulated via DNA sequences contents and their nucleosome-positioning patterns based on our in vitro findings.



http://ift.tt/2on3XUh

Data on cytotoxicity in HeLa and SU-DHL-4 cells exposed to DPB162-AE compound

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Mart Bittremieux, Katsuhiko Mikoshiba, Geert Bultynck
DPB162-AE is a valuable tool to study store-operated Ca²⁺ entry (SOCE), as this compound was developed as a 2-APB analog that inhibits SOCE more potently and more selectively than 2-APB itself. In addition to this, we showed that, in some conditions, DPB162-AE can deplete the endoplasmic reticulum Ca²⁺ stores in intact cells, including the cervical carcinoma HeLa cell line and the diffuse large B-cell lymphoma SU-DHL-4 cell line. Here, we present data regarding the toxicity of DPB162-AE in HeLa and SU-DHL-4 cells. For further interpretation of the data presented in this article, please see the research article 'DPB162-AE, an inhibitor of store-operated Ca²⁺ entry, can deplete the endoplasmic reticulum Ca²⁺ store' (M. Bittremieux, J. V. Gerasimenko, M. Schuermans, T. Luyten, E. Stapleton, K.J. Alzayady, et al., 2017) [1].



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Characterization and distribution of mechanically competent mineralized tissue in micropores of β-tricalcium phosphate bone substitutes

Publication date: Available online 1 April 2017
Source:Materials Today
Author(s): Marc Bohner, Gamal Baroud, Anke Bernstein, Nicola Döbelin, Laetitia Galea, Bernhard Hesse, Roman Heuberger, Sylvain Meille, Pascal Michel, Brigitte von Rechenberg, Jorge Sague, Howard Seeherman
Although bone formation around and within implants has been intensively studied, the role of pores and pore geometry is still debated. Notwithstanding studies reporting the formation of bone and bone components within pores as small as a few micrometers ('micropores'), bone ingrowth is believed to only occur in pores larger than 100μm ('macropores'). A thorough analysis of 10 different porous β-tricalcium phosphate cylinders (Ø: 8mm; L: 13mm) implanted for 2–24 weeks in an ovine model demonstrates ingrowth of mineralized tissue (MT) in pores as small as 1μm. This tissue contained calcium phosphate, collagen, and interconnected cells. It formed within the first 3–4 weeks of implantation, extended over several hundred micrometers within the ceramic, and contributed to the majority of the early MT formation (including bone) in the defect. The indentation stiffness of the MT-ceramic composite was significantly higher than that of bone and MT-free ceramic. The presented results substantiate the importance of micropores for optimal bone healing, particularly at early implantation times.

Graphical abstract

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Modulation of Motor Cortex Excitability Predicts Antidepressant Response to Prefrontal Cortex Repetitive Transcranial Magnetic Stimulation

Publication date: Available online 31 March 2017
Source:Brain Stimulation
Author(s): Albino J. Oliveira-Maia, Daniel Press, Alvaro Pascual-Leone
BackgroundRepetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use.ObjectiveWe report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS.MethodsFifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. MEP's were induced with single TMS pulses and measured using surface electromyography. MEP modulation was calculated as the change of mean MEP amplitude after MC rTMS.ResultsMEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. This was found both in univariate analyses (Spearman regression: rho=0.43, p<0.005) and a multivariable linear regression model (β=0.25, p<0.0001) controlling for baseline depression severity, age and resting motor threshold.ConclusionsThese findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS.



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Post-Obstructive Cyst Formation in Pancreas and Cystic Acinar Transformation: Are They Same?

Publication date: Available online 1 April 2017
Source:Pathology - Research and Practice
Author(s): Xuchen Zhang, Hongfa Zhu, Xiu Yang, Volkan N. Adsay, Dhanpat Jain
Pancreatic "acinar cell cystadenoma" (PACA) is a rare benign pancreatic cystic lesion showing acinar cell differentiation. The neoplastic nature of PACA has been questioned and its exact pathogenesis remains unclear. To investigate that acinar cell differentiation is a non-specific metaplastic phenomenon that can occur in pancreatic ductal system, especially when chronically inflamed and dilated, and doesn't necessarily imply an acinar cell neoplasm, we retrospectively analyzed cases diagnosed as PACA and cases with post-obstructive cystic dilatation of pancreatic ducts for acinar cell differentiation using immunohistochemistry for trypsin. The etiology of obstruction was microscopic periductal pancreatic neuroendocrine tumors (PanNET) and pancreatic ductal adenocarcinomas (PDAC). All cases of post-obstructive cystic dilatation showed multiple varying sized cysts distal to the obstruction with histologic findings virtually identical to PACAs. The cysts in both conditions were lined by a single layer of non-dysplastic flattened to columnar ductal-type epithelium with areas of acinar cell differentiation. Trypsin immunohistochemistry confirmed presence of acinar cell differentiation in all cases of post-obstructive cysts and PACAs. Our results suggest that acinar cell differentiation is common in post-obstructive cyst formation, and changes are identical to PACAs. These findings further support the notion that PACA is a benign non-neoplastic cystic lesion with acinar cell differentiation. The findings also suggest that in cases with histology resembling "PACA" or showing diffuse ductal cystic dilation, careful gross examination should be carried out for a proximal obstructive lesion, which can be subtle and easily be missed on initial examination.



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Supramacroparticulate PE in 6 different joint endoprostheses localisations: An indicator for PE damage?

Publication date: Available online 31 March 2017
Source:Pathology - Research and Practice
Author(s): Simon Krenn, Marc Thomsen, Sylvia Usbeck, Leslie F. Scheuber, Friedrich Boettner, Manfred Georg Krukemeyer, Monika Huber, Jan Philippe Kretzer, Thorsten Gehrke, Veit Krenn
In the histopathological particle algorithm polyethylene (PE) particles with maximum lengths of more than 100μm – called PE supramacroparticles – are identified exclusively for knee joint and hip prostheses. However, a definitive characterisation, detection in all joint localisations and a causal clarification of the pathogenesis are lacking. In this study a total of 175 SLIM (synovial-like interface membrane) cases with PE supramacroparticles of knee joint prostheses (n=89), hip joint prostheses (n=44), ankle joint prostheses (n=36) and prostheses in three localisations of the upper extremities (n=6) were systematically investigated. The arithmetic mean of the particle length varied greatly within the prosthesis types. This had a significant positive correlation with the prosthesis lifetime and negative correlation with the date of implantation. It can be concluded that both the lifetime and the time of implantation have an influence on the particle length. The prostheses with supramacroparticulate damage moreover showed a clearly reduced survival rate compared with other data published on the prosthesis lifetime. The material wear therefore could not be attributed solely to the usual fatigue factors. Since loosening of the prostheses, decentring of the PE components or damage to the PE inlay existed in all cases, mechanical dysloading seems to be the most probable cause of PE supramacroparticle genesis. Due to the striking length and for demarcation from PE macroparticles, the term supramacroparticulate PE is proposed for a length of more than 100μm. In the extended histopathological particle algorithm supramacroparticulate PE has been included in the macroparticles category and should be taken into account and interpreted causally in histopathological diagnostics of joint prosthesis failure.



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