Liaison between Heme Metabolism and Bioenergetics Pathways-A Multimodal Elucidation for Early Diagnosis of Oral Cancer

Publication date: Available online 4 January 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Ripon Sarkar, Kabita Chaterjee, Durbadal Ojha, Bijurica Chakraborty, Sanghamitra Sengupta, Debprasad Chattopadhyay, Chirasree RoyChaudhuri, Ananya Barui
Metabolic alterations of oral epithelial cells under oxidative stress are important signatures for early diagnosis of oral cancer. Amongst different metabolic alterations, non-invasive photo-diagnostic methods have been extensively used for determining cellular heme metabolism and accumulation of protoporphyrin IX (PpIX) under administration of suitable photosensitizer. In this study, we report these metabolic alterations by direct analysis of oral exfoliated cells obtained from individuals with prolonged smoking habit without the exogenous administration of any photosensitizer. The relative expression level of relevant biomolecules of study groups were compared with clinically diagnosed and histopathologically confirmed leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC) patients. The energy imbalance and variation in 'redox ratio' were examined through spectroscopic studies which showed an increasing trend (p < 0.001) in smokers to OSCC groups in comparison to nonsmoker control. Gene expression of important intermediates of the heme metabolic pathway (viz. 5-aminolevulinate synthase 1 (ALAS1), Ferrochelatase (FECH), hemeoxygenase 1 (HO-1) and ATP binding cassette subfamily G member 2 (ABCG2)) which affect production of PpIX was assessed. Relative mRNA level of ALAS1 and HO1 was upregulated whereas mRNA level of other genes (viz. FECH and ABCG2) were found to be downregulated in smokers as well as in cancer groups. Outcome of different spectroscopic studies on exfoliated cells (viz. fluorescence, atomic absorption and Fourier transform infrared spectroscopy) corroborated with the expression of biomarkers related to cellular endogenous metabolism related to heme cycle. Upshot of this study indicates significant alterations in endogenous metabolic products, and cellular functional groups in oral epithelial cells among the study groups. Our study for the first time reports a strong possibility of diagnosis of early cancer signatures amongst habitual smokers by direct and non-invasive assessment of metabolic status of oral epithelial cells without exogenous administration of photosensitizers. The knowledge accrued from the study may guide clinicians in precise detection of precancer trend in the susceptible population through a noninvasive rapid screening method.

Graphical abstract

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Antimicrobial properties of a new type of photosensitizer derived from phthalocyanine against planktonic and biofilm forms of Staphylococcus aureus

Publication date: Available online 4 January 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Yiru Gao, Bingjie Mai, Ao Wang, Min Li, Xiaobing Wang, Kun Zhang, Quanhong Liu, Shaohua Wei, Pan Wang
BackgroundBacterial infection is a common clinical problem. Community-associated Staphylococcus aureus (S. aureus) infections can cause extensive tissue damage and necrosis. Photodynamic antimicrobial chemotherapy (PACT) has recently attracted attention as a feasible alternative to bacterial therapy. Octa-cationic zinc phthalocyanines are newly identified photosensitizers derived from phthalocyanines bearing 1, 2-ethanediamine groups and quaternized derivatives with different numbers of positive charges (ZnPcⁿ⁺, n = 4 or 8). Here we report the antimicrobial effects of ZnPcⁿ⁺-mediated PACT on planktonic and biofilm cultures of S. aureus.MethodsZnPcⁿ⁺ uptake was detected by photometry after alkaline lysis. Dark-toxicity and light-mediated antimicrobial effects of the drug was determined by the plate count method. The production of intracellular reactive oxygen species (ROS) was detected by flow cytometry. SYTO 9 and propidium iodide (PI) were used to detect the bacterial cell membrane permeability. DNA damage after ZnPcⁿ⁺-PACT was analyzed by flow cytometry and PI staining. The destruction of biofilm was evaluated by scanning electron microscope (SEM).ResultsThe study of uptake showed that the relative fluorescence intensity of ZnPcⁿ⁺ in S. aureus peaked at 15 min. Generation of reactive oxygen species (ROS) by ZnPcⁿ⁺ was enhanced in PACT treatment groups. SYTO 9 and PI staining indicated that cell membrane was damaged. Flow cytometry and PI staining revealed DNA damage. Biofilms were damaged in PACT treatment groups.ConclusionsOur results suggest that light-activated ZnPcⁿ⁺ can efficiently inhibit planktonic and biofilm cultures of S. aureus.



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Single and combined effects of photodynamic therapy and antibiotics to inactivate Staphylococcus aureus on skin

Publication date: Available online 4 January 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Tatiana Moura Branco, Nádia Castanho Valério, Vânia Isabel Rodrigues Jesus, Cristina Jesus Dias, Maria G.P.M.S. Neves, Maria A.F. Faustino, Adelaide Almeida
In this study, the effect of antimicrobial photodynamic therapy (aPDT) and aPDT combined with antibiotics to inactivate Staphylococcus aureus in vitro and ex vivo was compared. The tetracationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (Tetra-Py⁺-Me) was used to inactivate S. aureus in phosphate buffer solution (PBS) (in vitro) and in pork skin artificially contaminated with S. aureus (ex vivo). The results showed an efficient reduction of 8 log in PBS, after 180 min of irradiation under white light at 4.0 mW cm⁻² with Tetra-Py⁺-Me at 5.0 μM. When aPDT was repeated in the presence of antibiotics, an increased effect was observed with ampicillin at 0.5 and 1.0 μg mL⁻¹ (MIC 0.25 μg mL⁻¹) – the full inactivation (8 log) occurred faster, respectively, after 60 and 30 min of irradiation. In ex vivo, a reduction of ∼4 log of S. aureus was observed after 180 min with 50 μM of Tetra-Py⁺-Me at 150 mW cm⁻², but this efficiency increased significantly with the application of three successive light cycles (reduction to the detection limit ∼6 log). The photoinactivation efficiency observed in ex-vivo was also significantly improved when the experiments with 50 μM of Tetra-Py⁺-Me were repeated in the presence of 5.0 μg mL⁻¹ of ampicillin (inactivation of ∼5.6 log). The results showed that aPDT is an effective approach to control S. aureus infection in skin, inactivating the bacterium to the detection limit after three successive cycles of treatment or after one cycle by using the combination aPDT and ampicillin.

Graphical abstract

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Comparative risk assessment and cessation information seeking among smokeless tobacco users

Publication date: May 2018
Source:Addictive Behaviors, Volume 80
Author(s): Jungmi Jun, Xiaoli Nan
IntroductionThis research examined (1) smokeless tobacco users' comparative optimism in assessing the health and addiction risks of their own product in comparison with cigarettes, and (2) the effects of comparative optimism on cessation information-seeking.MethodsA nationally-representative sample from the 2015 Health Information National Trends Survey (HINTS)-FDA was employed.ResultsThe analyses revealed the presence of comparative optimism in assessing both health and addiction risks among smokeless tobacco users. Comparative optimism was negatively correlated with most cessation information-seeking variables. Health bias (the health risk rating gap between the subject's own tobacco product and cigarettes) was associated with decreased intent to use cessation support. However, the health bias and addiction bias (the addiction risk rating gap between the subject's own tobacco product and cigarettes) were not consistent predictors of all cessation information-seeking variables, when covariates of socio-demographics and tobacco use status were included. In addition, positive correlations between health bias and past/recent cessation-information searches were observed.ConclusionsOptimisic biases may negatively influence cessation behaviors not only directly but also indirectly by influencing an important moderator, cessation information-seeking. Future interventions should prioritize dispelling the comparative optimism in perceiving risks of smokeless tobacco use, as well as provide more reliable cessation information specific to smokeless tobacco users.



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Obituary Johannes J. ("Jon") van Rood

Publication date: Available online 3 January 2018
Source:Current Opinion in Immunology
Author(s): Hidde Ploegh




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Open Surgical Conversion After Endovascular Aortic Aneurysm Repair

Publication date: Available online 4 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Stavros K. Kakkos, Eric L. Verhoeven




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Mid-term Outcomes of Endovascular Repair of Ruptured Thoraco-abdominal Aortic Aneurysms with Off the Shelf Branched Stent Grafts

Publication date: Available online 4 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Kiattisak Hongku, Björn Sonesson, Katarina Björses, Jan Holst, Timothy Resch, Nuno V. Dias
ObjectiveTo assess the mid-term outcomes and feasibility of branched endovascular repair (b-EVAR) of ruptured thoracoabdominal aortic aneurysms (rTAAAs).MethodsAll patients undergoing b-EVAR of rTAAAs between 2011 and 2016 were included. Pre-, intra and postoperative imaging was reviewed to assess technical success, outcomes, and feasibility of b-EVAR in the emergent setting.ResultsEleven emergency b-EVAR of rTAAAs (10 aneurysms and 1 chronic dissection) were performed using off-the-shelf (OTS) branched stentgrafts. Only 18% of patients complied to the anatomical instruction-for-use of the OTS device; a small aortic lumen and occluded target vessels were the main violations. Median operative time was 430 (IQR 395-629) minutes. Technical failure was 36% including one intraoperative death, one target vessel catheterization failure, one type Ia and one type III endoleak. Thirty-day mortality was 27%. Only early re-intervention was for the type Ia endoleak. Spinal cord ischemia occurred in 4 patients (30%), of which 2 recovered completely. Median clinical follow-up were 15 (IQR 7-39) months respectively. The median clinical follow-up index (FUI) was 0.65 (0.32–0.95). Overall survival was 75 ± 21.7% at 18 months. Four branch occlusions occurred; one renal stent occlusion led to permanent hemodialysis. Branch patency was 87.5 ± 8.3% and 72.2 ± 12% at 1 and 2 years, respectively. One stentgraft migrated but no late major endoleak occurred.ConclusionEmergency b-EVAR of rTAAA with OTS device is feasible despite a low anatomical suitability. With proper adjunctive procedures, it can be offered to most hemodynamically stable patients. These time-consuming complex procedures are not suitable for unstable patients. Often the procedure is done as life-saving in the emergency setting and reinterventions may be needed later. Consequently, the success rates are lower than in the elective setting. These results need to be confirmed by larger studies and longer follow-up.



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Histologic and immunohistochemical differences between hereditary and sporadic diffuse gastric carcinoma

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Hee Eun Lee, Thomas C. Smyrk, Lizhi Zhang
We aimed to identify histopathologic features unique in hereditary diffuse gastric cancer (HDGC) by comparing with its sporadic counterpart (SDGC). 11 patients with confirmed CDH1 mutation who were found to have HDGC in a prophylactic total gastrectomy were collected. Median age of HDGC patients was 39 years (range 24-57). All HDGC cases had intramucosal signet ring cell carcinoma. Twenty-three invasive tumor foci from 7 patients with HDGC were available for ancillary studies, and we evaluated each focus separately. Almost all foci (20/23) showed two distinct tumor cell populations, namely large signet ring cells and small signet ring cells. The large cells were located just beneath the surface epithelium and were positive for mucicarmine and pCEA while the small cells were found in the deeper lamina propria and were mostly negative for mucicarmine and pCEA. A subset of small cells (6 foci from two resected stomachs) showed poorly-differentiated morphology with p16 positivity. All other tumor cells with well-differentiated signet ring cell morphology were negative for p16. In contrast, 18 of 20 SDGCs were positive for p16. In addition, all HDGCs were negative for CDX2 while 19 of 20 SDGCs were positive. We propose that there are three distinct tumor cell populations in HDGC: well-differentiated large cells, well-differentiated small cells, and poorly-differentiated small cells, and that the latter group with aberrant p16 expression may represents a more aggressive phenotype. The absence of CDX2 in HDGC suggests that it may develop along a carcinogenetic pathway different from that of SDGC.



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MVP Immunohistochemistry is a Useful Adjunct in Distinguishing Leiomyosarcoma from Leiomyoma and Leiomyoma with Bizarre Nuclei

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Nicholas J. Lintel, Stephen A. Luebker, Subodh M. Lele, Scott A. Koepsell
Morphologically, distinguishing between leiomyoma (LM) and leiomyosarcoma (LMS) is not always straightforward, especially with benign variants such as bizarre leiomyoma (BLM). To identify potential markers of malignancy in uterine smooth muscle tumors, proteomic studies were performed followed by assessment of protein expression by immunohistochemistry. Archival formalin-fixed paraffin-embedded (FFPE) tissues from tumors (n=23) diagnosed as LM, BLM and LMS (using published criteria) were selected for the study. Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was applied to pooled samples of FFPE LM and LMS tumor tissue to assay the relative protein quantities and look for expression patterns differentiating the two tumor types. A total of 592 proteins were quantified, and 10 proteins were differentially expressed between LM and LMS. Select proteins were chosen for evaluation by immunohistochemistry (IHC) based on antibody availability and biologic relevance in the literature. IHC was performed on a tissue microarray and intensity was evaluated using imaging software. Major vault protein (MVP) and catechol O-methyltransferase (COMT) had 3.05 and 13.94 times higher expression in LMS relative to LM by SWATH-MS respectively. By IHC, MVP (clone 1014, Santa Cruz Biotechnology, Dallas TX) was found to be 50% sensitive and 100% specific when comparing LMS to LM. COMT (clone FL-271, Santa Cruz Biotechnology, Dallas TX) had a sensitivity of 38% and a specificity of 88%. 6/7 BLM had expression of MVP similar to LM. Immunohistochemical staining for MVP is a useful adjunct in distinguishing LMS from LM and BLM in difficult cases.



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Classic Hodgkin lymphoma with osseous involvement mimicking Langerhans cell histiocytosis in a child

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Kazuhiko Kuwahara, Ko Kudo, Akiko Yashima-Abo, Kosuke Katayama, Keiko Kojima, Kiyoshi Tone, Etsuro Ito, Atsuko Nakazawa, Hideto Iwafuchi, Akira Kurose
Hodgkin lymphoma (HL) commonly presents the superficial lymphadenopathy. In addition, HL cells can arise in various organs including the liver and spleen as an extranodal lymphoma. HL in bone is unusual at the initial diagnosis, although some cases show late stage localization of lymphoma cells to bone. We report the rare case of a young patient with cranial bone classic HL, presumably originating from the skull without any involvement of lymph nodes. As the main clinical manifestation was only tumor mass in the skull without osteoscopic pain, the tentative diagnosis of Langerhans cell histiocytosis was histologically confirmed by an excisional biopsy. Before the final pathological diagnosis as classic HL, we noticed several small lesions in extranodal regions through systemic surveys, suggesting that the cranial lesion appeared antecedent to those lesions. This is a rare and instructive case of cranial bone HL for which a histological diagnosis has been meticulously made.



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Effective use of Twitter and Facebook in pathology practice

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Pembe Oltulu, Abul Ala Syed Rifat Mannan, Jerad M. Gardner
Social networking has become a part of daily life for most people. In the era of globalization, it has become indispensable for effective communication between friends and peers across the world. Today, social media use is not only restricted to our personal lives; it is becoming increasingly incorporated into our professional lives, as well. Social media platforms are rapidly becoming a necessary tool for medical professionals. Apt use of social media platforms can revolutionize scientific communication and collaboration. Pathologists are increasingly counted among Facebook's 2 billion users and Twitter's 328 million members. Social media can be a powerful tool not only for individual career progression, but also for raising the public profile of the specialty of pathology. It is now possible for us to reach out to millions of people, simultaneously and instantaneously, just by touching a screen. Real time interactions between physicians, across geographic borders and subspecialty borders, will undeniably open unexplored avenues for effective communication, consultation, research collaboration, and education. Knowledge sharing through social media will immensely enrich and grow our careers as pathologists; it will also enlighten the public and physicians of other specialties as to the crucial role of pathologists in patient care. We discuss the uses of Facebook and Twitter in modern day pathology, its implication in routine daily practice, pros and cons, and tips for effective social media use by pathologists.



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Tumor budding as a novel predictor of occult metastasis in cT2N0 tongue squamous cell carcinoma

Publication date: Available online 4 January 2018
Source:Human Pathology
Author(s): Junki Sakata, Keisuke Yamana, Ryoji Yoshida, Yuichiro Matsuoka, Kenta Kawahara, Hidetaka Arita, Hikaru Nakashima, Masashi Nagata, Akiyuki Hirosue, Sho Kawaguchi, Shunsuke Gohara, Yuka Nagao, Akimitsu Hiraki, Masanori Shinohara, Ryo Toya, Ryuji Murakami, Hideki Nakayama
Occult neck metastasis is an important prognostic factor in patients with tongue squamous cell carcinoma (TSCC) who are deemed clinically negative for neck metastasis. The purpose of this study was to identify predictive factors for occult neck metastasis arising from TSCC and to determine patient prognosis. Ninety-seven patients with cT2N0 TSCC who underwent surgical resection of their primary lesion as initial therapy were enrolled in this retrospective study. Cutoff values for depth of invasion (≥3.3 mm) and the tumor budding score (≥4) were determined using receiver operator characteristic analyses. Univariate and multivariate analyses revealed that a tumor budding score ≥4 is a significant independent predictive factor for the occurrence of occult neck metastasis, which in turn is a significant independent prognostic factor. When evaluating tumor budding, we demonstrated greater inter-observer and intra-observer agreement when using immunohistochemical staining for cytokeratin AE1/AE3 than with hematoxylin and eosin staining (HE). We conclude that the evaluation of tumor budding is effective for identifying populations at high risk of occult neck metastasis, which will enable the planning of appropriate therapeutic strategies for patients with cT2N0 TSCC. Furthermore, cytokeratin staining is recommended over HE staining for simpler and more accurate evaluation of tumor budding.



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Bisphenol A stimulates adrenal cortical cell proliferation via ERβ-mediated activation of the sonic hedgehog signalling pathway

Publication date: Available online 4 January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Samantha Medwid, Haiyan Guan, Kaiping Yang
We previously demonstrated that prenatal exposure to bisphenol A (BPA) resulted in increased adrenal gland weight independent of changes in plasma ACTH levels in adult mouse offspring. This finding suggested that BPA exposure likely had a direct effect on adrenal development. Given that (1) sonic hedgehog (Shh) signaling is essential for adrenal development; (2) deletion of the Shh gene in mice results in adrenal hypoplasia; (3) BPA is known to signal through estrogen receptor β (ERβ); and (4) ERβ is highly expressed in adrenal glands; we hypothesized that BPA stimulates adrenal cell proliferation via ERβ-mediated activation of the Shh pathway. To test this hypothesis, the human adrenal cell line, H295A cells, was used as an in vitro model system. Our main findings were: (1) BPA increased cell number and protein levels of proliferating cell nuclear antigen (PCNA; a universal marker of cell proliferation), cyclin D1 and D2 (key proliferation factors), as well as Shh and its key transcriptional regulator Gli1; (2) cyclopamine, a Shh pathway inhibitor, blocked these stimulatory effects of BPA on cell proliferation; (3) BPA increased the nuclear translocation of ERβ; and (4) the ERβ-specific agonist DPN mimicked while the ERβ-specific antagonist PHTPP abrogated the stimulatory effects of BPA on cell proliferation and Shh signaling. Taken together, these findings demonstrate that BPA stimulates adrenal cell proliferation likely through ERβ-mediated activation of the Shh signaling pathway. Thus, the present study provides novel insights into the molecular mechanisms underlying our previously reported BPA-induced aberrant adrenal phenotype.



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The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro

Publication date: Available online 4 January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Lucie Rárová, David Sedlák, Jana Oklestkova, Jana Steigerová, Johanna Liebl, Stefan Zahler, Petr Bartůněk, Zdeněk Kolář, Ladislav Kohout, Miroslav Kvasnica, Miroslav Strnad
We report the synthesis and detailed biological study of the synthetic brassinosteroid analog 2α,3α-dihydroxy-6-oxo-5α-androstan-17β-yl N-(tert-butoxycarbonyl)-D,L-valinate (BR4848). The panel of cancer cell lines was used for characterization of its antiproliferative activity, yet had no adverse effects in normal human fibroblasts. In HeLa cells, BR4848-induced apoptosis was accompanied by increase of apoptotic subG1 cells, PARP-1 and caspase-7 fragmentation, downregulation of Bcl-2 and Mcl-1, an increase in caspase activity and G2/M phase cell cycle arrest. Antiproliferative properties of BR4848 were exhibited by inhibition of phosphorylation of Akt, Erk1/2 and FAK. Furthermore, the developed analog exhibited in vitro antiangiogenic activity in human umbilical vein endothelial cells (HUVECs). BR4848-induced apoptosis accompanied with G2/M arrest was detected in endothelial cells. BR4848 also inhibited adhesion, tube formation and migration of endothelial cells by inhibition of FAK, Erk 1/2, CDK5, VEGFR2, TNFα-stimulated production of IL-6, angiopoietin-2 and Jagged1. Finally, BR4848 did not modulate the activity nor nuclear translocation of any of the steroid receptors (ERα, ERβ, AR, MR and PR) included in reporter cell-based assays, which excludes the genomic activity of steroid receptors as a contributing factor to the observed biological activities of BR4848.



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Utility of a Standardized Fourth-Year Medical Student Surgical Preparatory Curriculum: Program Director Perceptions

Publication date: Available online 3 January 2018
Source:Journal of Surgical Education
Author(s): Melissa K. Stewart, Rebecca C. Henry, Jesse M. Ehrenfeld, Kyla P. Terhune
ObjectiveEach July, surgical interns arrive to residency with variable skills, knowledge, and clinical experience. To standardize and improve intern preparation, the American College of Surgeons (ACS), Association of Program Directors in Surgery, and Association for Surgical Education developed a pilot Resident Prep Curriculum (RPC). To date, no studies have analyzed these efforts. We aimed to discern program director (PD) perceptions of RPC participants as an initial means of analysis.DesignA 17-question PD survey was designed to assess variable preparedness and performance between RPC participants and nonparticipants. PDs reporting matriculation of a RPC participant were first asked to globally compare the participant to nonparticipants. Using a 5-point Likert scale, PDs were then asked to compare participants to nonparticipants in 7 distinct categories, which were based on course objectives that parallel the Accreditation Council for Graduate Medical Education competencies. Descriptive statistics and tests of significance were performed to evaluate the responses.ParticipantsThe survey was sent via electronic mail to 245 accredited general surgery residency PDs.ResultsA total of 103 (42.0%) PDs responded. Of the respondents, 27 (26.2%) reported matriculation of a RPC participant. When assessing efficiency in intern responsibilities, 26.9% of PDs noted participant advantage, and when gauging comfort in intern-role, 25.9% of PDs reported participant benefit. Across the 7 queried course objectives, there was a statistically significant improvement in the technical skill domain (p = 0.007) and a nonsignificant trend toward improvement in several of the other 6 domains: interpersonal skills (p = 0.055), medical knowledge (p = 0.067), patient care (p = 0.081), systems-based practice (p = 0.085), problem-based learning (p = 0.106), and professionalism (p = 0.357).ConclusionsPD perceptions revealed global advantage to RPC participation Furthermore, 1/4 of the time and specific competency performance showed substantial improved performance in technical skills. Survey timing and washout may bias this study, and the results should be compared to learner and senior resident perceptions, where observations may be more granular.



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Temporal and geospatial trends of pediatric cancer incidence in Nebraska over a 24-year period

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): P.A. Farazi, S. Watanabe-Galloway, L. Westman, B. Rettig, P. Hunt, R. Cammack, J.W. Sparks, D.W. Coulter
BackgroundData from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009–2013. Further investigation could help understand these patterns.MethodsThis retrospective cohort study investigated pediatric cancer (0–19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990–2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, location–allocation analysis (LAA) was performed to identify a site for the placement of a medical center to best accommodate rural pediatric cancer cases.ResultsThe AAR of pediatric cancers was 173.3 per 1,000,000 in Nebraska compared to 167.1 per 1,000,000 in SEER. The AAR for lymphoma was significantly higher in Nebraska (28.1 vs. 24.6 per 1,000,000; p = 0.009). For the 15–19 age group, the AAR for the 3 most common pediatric cancers were higher in Nebraska (p < 0.05). Twenty-three counties located >2 h driving distance to care facilities showed at least a 10% higher incidence than the overall state AAR. GIS mapping identified a second potential treatment site that would alleviate this geographic burden.ConclusionsRegional differences within Nebraska present a challenge for rural populations. Novel use of GIS mapping to highlight regional differences and identify solutions for access to care issues could be used by similar states.



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Subsite- and stage-specific colorectal cancer trends in Estonia prior to implementation of screening

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Kaire Innos, Heigo Reima, Aleksei Baburin, Keiu Paapsi, Tiiu Aareleid, Jaan Soplepmann
BackgroundThe occurrence of colorectal cancer (CRC) in Estonia has been characterised by increasing incidence, low survival and no screening. The study aimed to examine long-term incidence and survival trends of CRC in Estonia with specific focus on subsite and stage.MethodsWe analysed CRC incidence and relative survival using Estonian Cancer Registry data on all cases of colorectal cancer (ICD-10 C18–21) diagnosed in 1995–2014. TNM classification was used to categorise stage.ResultsAge-standardized incidence of colon cancer increased both in men and women at a rate of approximately 1% per year. Significant increase was seen for right-sided tumours, but not for left-sided tumours. Rectal cancer incidence increased significantly only in men and anal cancer incidence only in women. Age-standardized five-year relative survival for colon cancer increased from 50% in 1995–1999 to 59% in 2010–2014; for rectal cancer, from 38% to 56%. Colon cancer survival improved significantly for left-sided tumours (from 51% to 62%) and stage IV disease (from 6% to 15%). For rectal cancer, significant survival gain was seen for stage II (from 58% to 75%), stage III (from 34% to 70%) and stage IV (from 1% to 12%).ConclusionIn the pre-screening era in Estonia, increase in colon cancer incidence was limited to right-sided tumours. Large stage-specific survival gain, particularly for rectal cancer, was probably due to better staging and advances in multimodality treatment. Nonetheless, more than one quarter of new CRC cases are diagnosed at stage IV, emphasising the need for an efficient screening program.



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Building cancer registries in a lower resource setting: The 10-year experience of Golestan, Northern Iran

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Gholamreza Roshandel, Shahryar Semnani, Abdolreza Fazel, Mohammadreza Honarvar, MohammadHossein Taziki, SeyedMehdi Sedaghat, Nafiseh Abdolahi, Mohammad Ashaari, Mohammad Poorabbasi, Susan Hasanpour, SeyedAhmad Hosseini, SeyedMohsen Mansuri, Ataollah Jahangirrad, Sima Besharat, Abbas Moghaddami, Honeyehsadat Mirkarimi, Faezeh Salamat, Fatemeh Ghasemi-Kebria, Nastaran Jafari, Nesa Shokoohifar, Masoomeh Gholami, Alireza Sadjadi, Hossein Poustchi, Freddie Bray, Reza Malekzadeh
IntroductionThe Golestan population-based cancer registry (GPCR) was established in Golestan province, Northern Iran, within the Asian belt with predominance of upper-gastrointestinal cancers. We aimed to present the experiences of the registry in a resource–limited setting over the 10 years since its inception (2004–2013).MethodsThe GPCR was established as a research project to enable sustainable funding. A clear plan was developed for use of the GPCR data. New primary cancers were registered based on international standards, indices of data quality were routinely assessed and age-standardized incidence rates (ASR) per 100,000 person-years calculated using IARC's CanReg-5 software.ResultsOverall, 19807 new cancer cases were registered during the study period, an average of 1981 cases per annum, with overall ASR of 175.0 and 142.4 in males and females, respectively. The GPCR data suggested gastrointestinal and breast cancers as the most common malignancies in Golestan province. We observed increasing incidence rates of breast and colorectal cancers but declining trends of esophageal cancer. Overall, indices of data quality were within acceptable ranges.ConclusionsThe GPCR data have been included in IARC's Cancer Incidence in Five Continents series, were used in 21 research projects, and published as 30 research papers. The key ingredients for the successful establishment and maintenance of the GPCR included sustainable sources of funding, a clear action plan for the use of data as well as stakeholder cooperation across all areas of the registration. The GPCR may be considered as a model for planning population-based cancer registries in lesser-resourced settings.



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Patient education-level affects treatment allocation and prognosis in esophageal- and gastroesophageal junctional cancer in Sweden

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Gustav Linder, Fredrik Sandin, Jan Johansson, Mats Lindblad, Lars Lundell, Jakob Hedberg
BackgroundLow socioeconomic status and poor education elevate the risk of developing esophageal- and junctional cancer. High education level also increases survival after curative surgery. The present study aimed to investigate associations, if any, between patient education-level and treatment allocation after diagnosis of esophageal- and junctional cancer and its subsequent impact on survival.MethodsA nation-wide cohort study was undertaken. Data from a Swedish national quality register for esophageal cancer (NREV) was linked to the National Cancer Register, National Patient Register, Prescribed Drug Register, Cause of Death Register and educational data from Statistics Sweden. The effect of education level (low; ≤9 years, intermediate; 10–12 years and high >12 years) on the probability of allocation to curative treatment was analyzed with logistic regression. The Kaplan-Meier-method and Cox proportional hazard models were used to assess the effect of education on survival.ResultsA total of 4112 patients were included. In a multivariate logistic regression model, high education level was associated with greater probability of allocation to curative treatment (adjusted OR: 1.48, 95% CI: 1.08–2.03, p = 0,014) as was adherence to a multidisciplinary treatment-conference (adjusted OR: 3.13, 95% CI: 2.40–4.08, p < 0,001). High education level was associated with improved survival in the patients allocated to curative treatment (HR: 0.82, 95% CI: 0.69–0.99, p = 0,036).DiscussionIn this nation-wide cohort of esophageal- and junctional cancer patients, including data regarding many confounders, high education level was associated with greater probability of being offered curative treatment and improved survival.



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Established and suggested exposures on CLL/SLL etiology: Results from the CLL-MCC-Spain study

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Yolanda Benavente, Delphine Casabonne, Laura Costas, Claudia Robles, Esther Alonso, Esmeralda de la Banda, Eva Gonzalez-Barca, Rafael Marcos-Gragera, Javier Llorca, Adonina Tardón, José J. Monleon, Marta Aymerich, Elías Campo, Eva Gimeno-Vázquez, Gemma Castaño-Vinyals, Nuria Aragonés, Marina Pollán, Manolis Kogevinas, Sílvia de Sanjosé
IntroductionChronic Lymphocytic Leukemia (CLL/SLL) is the most common adult leukemia in Western countries. Although it is mostly an indolent disease it is still incurable and with limited knowledge in relation to its etiology. We aim to confirm and quantify established risk factors for CLL/SLL using a multi-center epidemiological population-based case-control study on CLL/SLL as well as to explore new exposures inconclusively associated with CLL/SLLMethodsUsing the framework provided by the large MCC-Spain case-control study, we explored established and suggested risk factors associated with CLL/SLL using data collected through a face-to-face interview. We estimated odds ratios (OR) and confidence intervals (CI) adjusted by basic confounders, in 1,845 controls from the general population and 560 CLL/SLL from 5 different Spanish regions.ResultsAmong the established risk factors, CLL/SLL cases were 3 times more likely to report first degree relatives with an hematological cancer (OR = 3.11, 95% CI 2.10 to 4.61) and nearly twice likely to have ever worked in agriculture (OR = 1.70, 95% CI = 1.34 to 2.16). New findings suggest that women with CLL/SLL were more likely to have central obesity (OR = 1.67 95% CI = 1.12 to 2.48). An inverse association was found for current alcohol consumption (p-trend<0.016) and for type II diabetes.ConclusionWe confirmed previous established risk factors for CLL/SLL. Among the new findings, further research of central obesity as preventable exposure and the treatment for type II diabetes are warranted.



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