bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of AAV2 and Hepatitis B Virus Integration Into Genome on Development of Hepatocellular Carcinoma in Patients with Prior Hepatitis B Virus Infection
Authors: Tatsuno Kenji , Midorikawa Yutaka , Takayama Tadatoshi , Yamamoto Shogo , Nagae Genta , Moriyama Mitsuhiko , Nakagawa Hayato , Koike Kazuhiko , Moriya Kyoji , Aburatani Hiroyuki
Published: July 2019

Purpose:

Hepatitis B viral (HBV) DNA is frequently integrated into the genomes of hepatocellular carcinoma (HCC) in patients with chronic HBV infection (chronic HBV, hereafter), whereas the frequency of HBV integration in patients after the disappearance of HBV (prior HBV, hereafter) has yet to be determined. This study aimed to detect integration of HBV and adeno-associated virus type 2 (AAV2) into the human genome as a possible oncogenic event.

Experimental Design:

Virome capture sequencing was performed, using HCC and liver samples obtained from 243 patients, including 73 with prior HBV without hepatitis C viral (HCV) infection and 81 with chronic HBV.

Results:

Clonal HBV integration events were identified in 11 (15.0%) cases of prior HBV without HCV and 61 (75.3%) cases of chronic HBV (P < 0.001). Several driver genes were commonly targeted by HBV, leading to transcriptional activation of these genes; TERT [four (5.4%) vs. 15 (18.5%)], KMT2B [two (2.7%) vs. five (6.1%)], CCNE1 [zero vs. one (1.2%)], CCNA2 [zero vs. one (1.2%)]. Conversely, CCNE1 and CCNA2 were, respectively, targeted by AAV2 only in prior HBV. In liver samples, HBV genome recurrently integrated into fibrosis-related genes FN1, HS6ST3, KNG1, and ROCK1 in chronic HBV. There was not history of alcohol abuse and 3 patients with a history of nucleoside analogue treatment for HBV in 8 prior HBV with driver gene integration.

Conclusions:

Despite the seroclearance of hepatitis B surface antigen, HBV or AAV2 integration in prior HBV was not rare; therefore, such patients are at risk of developing HCC.
Access to Cancer Precision Medicines in Switzerland: A Comparative Analysis (USA and EU) and Health Policy Implications
Authors: Vokinger Kerstin Noëlle , Muehlematter Urs Jakob , Rosemann Thomas J.
Published: July 2019

Social health insurance is mandatory in Switzerland and covers the costs of basic medical care. In general, with regard to medicines, the costs are only reimbursed if the drug is (1) approved by Swissmedic and (2) listed on the so-called Spezia­litätenliste (SL) by the Federal Office of Public Health (FOPH). However, the SL does not include all drugs. For non-SL drugs, cost coverage is only granted under exceptional circumstances. Absence of cost coverage by social health insurance is especially problematic for patients who need access to cancer drugs, since they are often costly. Even if such cancer drugs are approved by Swissmedic, patients may still lack access to them. Therefore, access to medicines includes two aspects: (1) the availability of a drug on the market (i.e., approval of a drug) and (2) inclusion on the SL (i.e., cost coverage by social health insurance). In this study, we aim to compare the current approval regulations for oncologic precision medicines in the USA, Europe, and Switzerland; to investigate cost coverage for these drugs in Switzerland; and to develop health policy implications about how access to these drugs could be improved in Switzerland.
Neutrophil Extracellular Traps
Authors: Thålin Charlotte , Hisada Yohei , Lundström Staffan , Mackman Nigel , Wallén Håkan
Published: July 2019

Recent studies have demonstrated a role of neutrophils in both venous and arterial thrombosis. A key prothrombotic feature of neutrophils is their ability to release web-like structures composed of DNA filaments coated with histones and granule proteins referred to as neutrophil extracellular traps (NETs). NETs were discovered over a decade ago as part of our first line of host defense against invading microorganisms. Although NETs have a protective role against pathogens, recent data suggest that an uncontrolled and excessive NET formation within the vasculature may contribute to pathological thrombotic disorders. In vitro studies suggest that NETs promote vessel occlusion by providing a scaffold for platelets, red blood cells, extracellular vesicles, and procoagulant molecules, such as von Willebrand factor and tissue factor. In addition, NET components enhance coagulation by both activating the intrinsic pathway and degrading an inhibitor of the extrinsic pathway (tissue factor pathway inhibitor). NET formation has, therefore, been proposed to contribute to thrombus formation and propagation in arterial, venous, and cancer-associated thrombosis. This review will describe animal and human studies suggesting a role of NETs in the pathogenesis of various thrombotic disorders. Targeting NETs may be a novel approach to reduce thrombosis without affecting hemostasis.
Endothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation
Authors: Zhuang Tao , Liu Jie , Chen Xiaoli , Zhang Lin , Pi Jingjiang , Sun Huimin , Li Li , Bauer Robert , Wang Haikun , Yu Zuoren , Zhang Qi , Tomlinson Brian , Chan Paul , Zheng Xiangjian , Morrisey Edward , Liu Zhongmin , Reilly Muredach , Zhang Yuzhen
Published: July 2019

Rationale:

Endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, transcriptional regulation of vascular endothelial inflammation has not been well clarified.

Objective:

This study aims to explore Foxp (forkhead box P) transcription factor 1 in regulation of endothelial homeostasis, atherogenesis, and its mechanisms.

Methods and Results:

To assess the importance of Foxp1 in atherosclerosis, Foxp1 expression was analyzed in human coronary artery and mouse artery, and we observed significant downregulation of Foxp1 in atherosclerotic and atherosusceptible endothelium. Endothelial-specific Foxp1 knockout mice (
Foxp1

ECKO

) were bred onto
Apoe

KO

mice to generate endothelial Foxp1-deletion hyperlipidemic model
Foxp1

ECKO

;Apoe

KO

, which displayed significant increases in atherosclerotic lesion formation in aortas and aortic roots with enhanced monocyte adhesion, migration, and infiltration into the vascular wall and formation of inflammatory lipid-laden macrophages. In contrast, endothelial-specific Foxp1 overexpression mice
Foxp1

ECTg

;Apoe

KO

exhibited reduced atherosclerotic lesion formation with less monocyte infiltration. Foxp1 was further identified as a gatekeeper of vessel inflammation by direct regulation of endothelial inflammasome components, including Nlrp3 (NLR [nucleotide-binding and leucine-rich repeat immune receptors] family pyrin domain containing 3), caspase-1, and IL (interleukin)-1β. Moreover, endothelial Foxp1 was found to be regulated by Klf2 (Kruppel-like factor 2). Oscillatory shear stress downregulated Foxp1 expression via repressing Klf2 expression in endothelium, and, therefore, promoted endothelial inflammasome activation, leading to atherosclerotic lesion formation. Simvastatin upregulated the reduced expression of Klf2 and Foxp1 in atherosusceptible vascular endothelium and alleviated vascular inflammation contributing to its inhibitory effect in atherosclerosis.

Conclusions:

These data are the first in vivo experimental validation of an atheroprotective role of endothelial Klf2 and Foxp1, which reveals a Klf2-Foxp1 transcriptional network in endothelial cells as a novel regulator of endothelial inflammasome activation for atherogenesis, therefore, provides opportunities for therapeutic intervention of atherosclerotic diseases and uncovers a novel atheroprotective mechanism for simvastatin.
Site Experience and Outcomes in the Trevo Acute Ischemic Stroke (TRACK) Multicenter Registry
Authors: Nogueira Raul G. , Haussen Diogo C. , Castonguay Alicia , Rebello Leticia C. , Abraham Michael , Puri Ajit , Alshekhlee Amer , Majjhoo Aniel , Farid Hamed , Finch Ira , English Joey , Mokin Maxim , Froehler Michael T. , Kabbani Mo , Taqi Muhammad A. , Vora Nirav , Khoury Ramy El , Edgell Randall C. , Novakovic Roberta , Nguyen Thanh , Janardhan Vallabh , Veznedaroglu Enrol , Prabhakaran Shyam , Budzik Ron , Frankel Michael R. , Nordhaus Brittany L. , Zaidat Osama O.
Published: July 2019

Background and Purpose—

It remains unclear how experience influences outcomes after the advent of stent retriever technology. We studied the relationship between site experience and outcomes in the Trevo Acute Ischemic Stroke multicenter registry.

Methods—

The 24 sites that enrolled patients in the Trevo Acute Ischemic Stroke registry were trichotomized into low-volume (<2 cases/month), medium-volume (2–4 cases/month), and high-volume centers (>4 cases/month). Baseline features, imaging, and clinical outcomes were compared across the 3 volume strata. A multivariable analysis was performed to assess whether outcomes were influenced by site volumes.

Results—

A total of 624 patients were included and distributed as low- (n=188 patients, 30.1%), medium- (n=175, 28.1%), and high-volume (n=261, 41.8%) centers. There were no significant differences in terms of age (mean, 66±16 versus 67±14 versus 65±15;
P
=0.2), baseline National Institutes of Health Stroke Scale (mean, 17.6±6.5 versus 16.8±6.5 versus 17.6±6.9;
P
=0.43), or occlusion site across the 3 groups. Median (interquartile range) times from stroke onset to groin puncture were 266 (181.8–442.5), 239 (175–389), and 336.5 (221.3–466.5) minutes in low-, medium-, and high-volume centers, respectively (
P
=0.004). Higher efficiency and better outcomes were seen in higher volume sites as demonstrated by shorter procedural times (median, 97 versus 67 versus 69 minutes;
P
<0.001), higher balloon guide catheter use (40% versus 36% versus 59%;
P
≤0.0001), and higher rates of good outcome (90-day modified Rankin Scale [mRS], ≤2; 39% versus 50% versus 53.4%;
P
=0.02). There were no appreciable differences in symptomatic intracranial hemorrhage or 90-day mortality. After adjustments in the multivariable analysis, there were significantly higher chances of achieving a good outcome in high- versus low-volume (odds ratio, 1.67; 95% CI, 1.03–2.7;
P
=0.04) and medium- versus low-volume (odds ratio, 1.75; 95% CI, 1.1–2.9;
P
=0.03) centers, but there were no significant differences between high- and medium-volume centers (
P
=0.86).

Conclusions—

Stroke center volumes significantly influence efficiency and outcomes in mechanical thrombectomy.
Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke
Authors: Burgos Adrian M. , Saver Jeffrey L.
Published: July 2019

Background and Purpose—

TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials.

Methods—

Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0–1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed.

Results—

Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0–1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, −1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end points: functional independence (modified Rankin Scale score, 0–2): crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, −3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93–1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority

Conclusions—

Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.
Paraschistura kermanensis, a new stone loach species from southeastern Iran (Teleostei: Nemacheilidae)
Authors: SAYYADZADEH GOLNAZ , TEIMORI AZAD , ESMAEILI HAMID REZA
Published: July 2019

Paraschistura kermanensis from the endorheic Kerman-Naein basin in Iran is distinguished from its closest congeners (P. abdolii, P. delvarii, P. kessleri and P. naumanni) by lacking scales on the flanks anterior to the dorsal-fin origin, having scales on the caudal peduncle, and having the pelvic-fin origin situated anterior to or below the vertical through the dorsal-fin origin. It is also characterised by six fixed diagnostic nucleotide substitutions and a K2P nearest neighbour distance of 4% to P. abdolii in the mtDNA COI barcode region.
Extratropical Cyclone Clouds in the GFDL Climate Model: Diagnosing Biases and the Associated Causes
Authors: Naud Catherine M. , Booth James F. , Jeyaratnam Jeyavinoth , Donner Leo J. , Seman Charles J. , Zhao Ming , Guo Huan , Ming Yi
Published: July 2019

The clouds in Southern Hemisphere extratropical cyclones generated by the GFDL climate model are analyzed against MODIS, CloudSat, and CALIPSO cloud and precipitation observations. Two model versions are used: one is a developmental version of “AM4,” a model GFDL that will utilize for CMIP6, and the other is the same model with a different parameterization of moist convection. Both model versions predict a realistic top-of-atmosphere cloud cover in the southern oceans, within 5% of the observations. However, an examination of cloud cover transects in extratropical cyclones reveals a tendency in the models to overestimate high-level clouds (by differing amounts) and underestimate cloud cover at low levels (again by differing amounts), especially in the post–cold frontal (PCF) region, when compared with observations. In focusing only on the models, it is seen that their differences in high and midlevel clouds are consistent with their differences in convective activity and relative humidity (RH), but the same is not true for the PCF region. In this region, RH is higher in the model with less cloud fraction. These seemingly contradictory cloud and RH differences can be explained by differences in the cloud-parameterization tuning parameters that ensure radiative balance. In the PCF region, the model cloud differences are smaller than either of the model biases with respect to observations, suggesting that other physics changes are needed to address the bias. The process-oriented analysis used to assess these model differences will soon be automated and shared.
Effect of modified nano zinc oxide on physico-chemical and antimicrobial properties of gamma-irradiated sawdust/epoxy composites
Authors: Abdel-Rahman Hoda A. , Awad Eman H. , Fathy Rasha M.
Published: July 2019

The present study aims to investigate the influence of modified zinc oxide nanoparticles content on the physico-chemical properties of sawdust/epoxy composite specimens. The results show an improvement in the mechanical properties in terms of flexural strength, impact strength, and hardness with increasing the modified zinc oxide nanoparticles content up to 5%, while the physical properties such as water absorption and thickness swelling percentages are decreased directly with increasing the content of modified zinc oxide. In addition, the behavior of irradiated composite specimens containing 5% modified zinc oxide nanoparticles at different gamma-irradiation doses, 10, 30, and 50 kGy, has been studied. The results indicate that the irradiated composite specimens at 10 kGy have better physico-chemical properties as compared to the unirradiated specimens. Furthermore, the antimicrobial properties of composite specimens containing 5% modified zinc oxide at 0 kGy and 10 kGy against different plant pathogenic fungi and bacteria are also discussed. The results demonstrate that the growth activity of fungi and bacteria on the composite specimens are reduced to a great extent as compared to the control composite specimens (0% of zinc oxide nanoparticles). Thermal behavior and morphology of the prepared specimens are detected using thermogravimetric analysis and scanning electron microscopy technique.
Realism and Resilience: An Inquiry Into the Helpfulness of Adopting an Existential Outlook
Authors: Alrofiai Fawaz , Bellingham Jessica , Gibson Paul S.
Published: July 2019

The form of sense making referred to as cognitive reappraisal has been shown to support resilience. This study, however, goes beyond replacing negative thoughts with more positive ones and investigates how some people are able to make sense of life events over time that are so significant they have the potential to cast a permanently negative shadow over the way a person feels and thinks about their life as a whole. Previous research has identified the supportive role that a religious or spiritual outlook can play, but we focus on whether and how the nonreligious outlook of Existentialism could support resilience. We conducted in-depth qualitative interviews over three months with nine informants, meeting with each informant five times, and present two illustrative narrative-based examples to demonstrate how it is possible to find support in an Existential outlook. Two key findings are highlighted as helpful Existential strategies: paying attention to what the totality of our moments add up to and constructing personal identities that are informed by authentic temporalizing. We also discovered, however, that our avowedly nonreligious informants were borrowing and repurposing some notions from spirituality, demonstrating a strong need to feel that things had turned out right in the end.
How Workplace Bullying Relates to Facades of Conformity and Work–Family Conflict: The Mediating Role of Psychological Strain
Authors: Liang Huai-Liang
Published: July 2019

This study examined the effects of workplace bullying on facades of conformity in the work domain and on work–family conflict in the family domain. In this research, workplace bullying is seen as a reality in organizations, and this study considers individuals’ judgments concerning various features of their workplace situations. Employees’ experiences of workplace bullying influence their creation of facades of conformity and crosses over to influence their partners’ family life through psychological strain. Psychological strain mediates the influence of workplace bullying on facades of conformity and on partners’ work–family life. A total of 569 employee–partner dyads from a large plastics corporation in Taiwan demonstrated significant relationships between workplace bullying and its outcomes at work and at home. The results of this study demonstrate that psychological strain is an important mechanism between workplace bullying and its consequences, both at work and at home. A time-lag study design and two different sources (i.e., employees and their married partners) were utilized to reduce common method bias in this study. The main theoretical and practical implications of the findings for future research are discussed.
The Influence of Geographic and Psychic Distance on Online Hotel Ratings
Authors: Phillips Paul , Antonio Nuno , de Almeida Ana , Nunes Luís
Published: July 2019

This study examines the relationship between distance measures and a Portuguese data set consisting of 34,622 online hotel reviews extracted from Booking.com and TripAdvisor written in Portuguese, Spanish, and English. Based on the country of origin of each review author, a geographic and a psychic distance measure is calculated for Portugal. Data and text mining analysis provides additional insights into online hotel ratings. The authors confirm that online travelers’ evaluations are multifaceted constructs displaying varying patterns of rating behavior among the traveler base. By investigating the contemporary relevance of geographic and psychic distance, a key finding of this study is that travelers with less distance both in terms of psychic and geographic distance give a lower rating score than travelers with greater distance. The inclusion of psychic and geographic distance is advocated as a salient aspect for future researchers and for those practitioners who wish to enhance hotel product and service features.
DNA Testing for Family Reunification and the Limits of Biological Truth
Authors: Lee Catherine , Voigt Torsten H.
Published: July 2019

As nation-states make greater efforts to regulate the flow of people on the move—refugees, economic migrants, and international travelers alike—advocates of DNA profiling technologies claim DNA testing provides a reliable and objective way of revealing a person’s true identity for immigration procedures. This article examines the use of DNA testing for family reunification in immigration cases in Finland, Germany, and the United States—the first transatlantic analysis of such cases—to explore the relationship between technology, the meaning of family, and immigration. Drawing on our analyses of archival records, government documents, and interviews with immigration stakeholders, we argue that DNA testing is not conclusive about the meaning of family. While the technology may facilitate decision making for both would-be immigrants and state officials, our study shows hesitancy among the latter to let DNA testing make the final determination. We introduce the concept of social validity—whether the interpretation of test results matches social or political meanings in a given local context—in order to make sense of the complexities and challenges of DNA testing in practice. We show that DNA testing is not just a technology of belonging or a way to claim citizenship rights. It may also enable exclusion and denial of rights.
Incidence, Mortality and Survival Trends of Cutaneous Melanoma in Umbria, Italy. 1978-82 and 1994-98
Authors: Stracci Fabrizio , Minelli Liliana , D'Alò Daniela , Fusco-Moffa Igino , Falsettini Elena , Cassetti Tiziana , Romagnoli Carlo , La Rosa Francesco
Published: July 2019

Many studies have reported increasing incidence rates of cutaneous melanoma during the last 30-40 years; the highest have been observed in Australia and New Zealand (27.9/100,000 among males and 25.0 among females) and in North America (10.9/100,000 among males and 7.7 among females). In Italy, from 1994-1998, in the areas covered by cancer registries (23% of Italian population), the incidence rate for males was 8.5 and for females, 1.9/100,000. The aim of the present study was to describe incidence, mortality and survival from cutaneous melanoma in the Umbrian population during the periods 1978-1982 and 1994-1998.
Statistical Interaction in the Survival Analysis of Early Breast Cancer using Registry Data: Role of Breast Conserving Surgery and Radiotherapy
Authors: Vinh-Hung Vincent , Burzykowski Tomasz , Van de Steene Jan , Voordeckers Mia , Lamote Jan , Storme Guy
Published: July 2019

Purpose

To identify subgroup effects that might influence the survival results of postoperative radiotherapy.

Patients and methods

Women selected from the Surveillance, Epidemiology, and End Results database, aged 40-69 years, with non-metastasized T1-T2 breast carcinoma, in whom axillary lymph node dissection was performed. Subgroup analyses were performed using proportional hazards models with interactions. Joint significance of subgroups was evaluated with the Wald test. Event was death from any cause.

Results

Statistically significant interactions were found between type of surgery (breast-conserving [BCS] or mastectomy [ME]), radiotherapy [RT], T stage, and extent of nodal involvement, but not between treatments and nodal examination. For each treatment combination, ME-no RT, ME+RT, BCS-no RT, BCS+RT, the mortality hazard ratios were respectively: 1, 1.12, 1.11, 0.78 in T1, 0-3 positive nodes; 2.45, 2.77, 2.71, 1.92 in T2, 4+ nodes; 1.31, 1.38, 1.33, 1.19 in T2, 0-3+ nodes; and 3.41, 2.79, 3.44, 2.40 in T2, 4+ nodes. The corresponding joint tests showed: in the absence of radiotherapy, no significant survival disadvantage for breast-conserving surgery vs mastectomy; with radiotherapy, significant survival advantage for breast-conserving surgery irrespective of stage and for mastectomy in T2, 4+ nodes. For mastectomy in less advanced stages receiving radiotherapy, excess breast cancer deaths suggested undocumented adverse selection. The corresponding result was considered inconclusive.

Conclusions

The analyses found subgroup effects that should be taken into account to interpret treatment results in breast cancer.
The Prognostic Value of p53 and c-erbB-2 Expression, Proliferative Activity and Angiogenesis in Node-Negative Breast Carcinoma
Authors: Erdem Özlem , Dursun Ayşe , Coşkun Uğur , Günel Nazan
Published: July 2019

Aims and background

p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma.

Methods

The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma.

Results

p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P <0.05). The mean MVD was 63.65 ± 29.1 and it correlated positively with histological grade and Ki-67 expression (P <0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant.

Conclusion

In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.
Cervical Sympathetic Chain Schwannoma Mimicking a Carotid Body Tumor: A Case Report
Authors: Uzun Lokman , Ugur Mehmet Birol , Ozdemir Huseyin
Published: July 2019

Carotid body tumor (CBT), the most common tumor of the carotid bifurcation, presents as a pulsatile mass. Cervical sympathetic chain (CSC) schwannomas are slow growing lesions originating from myelin-producing Schwann ceils. They may appear pulsatile due to the displacement of vascular structures by the non-vascular mass and thus may mimic a CBT. A case of CSC schwannoma masquerading as CBT in a 25-year-old woman is presented and discussed here.
Case Report of Synchronous Multicentric Osteosarcoma and Review of the Literature: The Importance of Autopsy for Diagnosis
Authors: Buzzoni Roberto , Torre Silvia Della , Cortinovis Diego , Catena Laura
Published: July 2019

Synchronous multicentric osteosarcoma is a rare entity with fewer than 100 well documented cases in the medical literature. The disease usually progresses rapidly in young patients and slightly slower in adults. We present a case of synchronous multicentric osteosarcoma with some peculiarities in a 73-year-old woman. The diagnosis was made after postmortem examination, which underlines the importance of this procedure. This case report is accompanied by a review of the literature.
Solitary Squamous Cell Carcinoma in the Kidney after Metachronous Development of Esophageal and Lung Cancer
Authors: Ku Ja Hyeon , Park Hyoung Keun , Lee Eunsik , Heo Dae Seog , Kim Hyeon Hoe
Published: July 2019

Solitary metastatic renal tumors are rarely encountered clinically. We report the case of a 65-year-old man who developed a solitary renal metastasis after undergoing an esophagectomy for esophageal cancer and subsequent lobectomy for lung cancer. The present case serves to demonstrate that careful follow-up is needed for esophageal cancer patients with cancer of another organ.
National Estimates of Cancer Patients Survival in Italy: A Model-Based Method
Authors: Inghelmann Riccardo , Grande Enrico , Francisco Silvia , De Angelis Roberta , Micheli Andrea , Verdecchia Arduino , Ferretti Stefano , Vercelli Marina , Ramazzotti Valerio , Pannelli Franco , Federico Massimo , De Lisi Vincenzo , Tumino Rosario , Falcini Fabio , Budroni Mario , Zanetti Roberto , Paci Eugenio , Crosignani Paolo , Zambon Paola , Capocaccia Riccardo
Published: July 2019

Aims and background

To provide model-based estimates of all cancers patient survival in Italy and in Italian large geographical areas (North-West, North-East, Center, South), where only partial coverage of cancer registries data is available, and to describe them in terms of time trends. Moreover, to measure the degree of representativeness of cancer patient survival obtained from Italian cancer registries data.

Methods

Relative survival in the four main Italian geographical areas was estimated by a parametric mixture model belonging to the class of “cure” survival models. Data used are from Italian cancer registries, stratified by sex, period of diagnosis and age. The Italian national survival was obtained as a weighted average of these area-specific estimates, with weights proportional to the number of estimated incident cases in every area. The model takes into account also differences in survival temporal trends between the areas.

Results

Relative survival for all cancers combined in Italian patients diagnosed in 1990-1994 was estimated to be higher in women (53%) than in men (38%) at 5 years from the diagnosis. The survival trend is increasing by period and decreasing creasing by age, both for men and women. The greatest gain in terms of survival was obtained by the elderly, with annual mean growth rates in the period 1978-1994 equal to 3.5% and 3.2% for men and women, respectively. More than 50% of the youngest cancer patients were “cured”, whereas for the elderly this proportion dropped to 15% and 25% for men and women, respectively. The South of Italy had the lowest survival and the North the most pronounced increase.

Conclusions

The obtained national survival estimates are similar, but not identical, to previously published estimates, in which Italian registries’ data were pooled without any adjustment for geographical representativeness. The four Italian areas have different survival levels and trends, showing variability within the country. The differences in survival between men and women may be explained by the different proportion of lethal cancers. Among males, most cases had a poor prognosis (lung and stomach cancers), whereas among females the largest proportion was made up of curable and less lethal cancers (breast cancer).
Hepatic Artery Administration of Docetaxel in Liver Metastases from Breast Carcinoma: A Feasibility Study
Authors: Cocconi Giorgio , Gamboni Alessandro , Gasparro Donatello , Leonardi Francesco , Salvagni Stefania , Vasini Giovanna , Larini Pietro , Marcato Carla , Camisa Roberta , Cascinu Stefano
Published: July 2019

Aims and background

Taxanes are largely metabolized and almost exclusively excreted in the feces by the liver through the biliary pathway, thus providing a rationale for investigating the activity of their hepatic artery delivery in case of liver metastases.

Study design

The aim of this study was to assess the feasibility of administering docetaxel via the hepatic artery in advanced breast cancer patients in whom the liver was the only or the predominant site of metastatic involvement. The dose was increased cycle by cycle in a prospective manner.

Results

Ten eligible patients were enrolled. The median administered dose in the last cycle was 65 mg/m2 (range, 40-100 mg/m2). The treatment was generally well tolerated, and only one patient stopped after two cycles because of toxicity. Four of the 9 eligible patients with assessable liver tumors achieved an objective response. After a median follow-up of 41 months, 4 of the 10 eligible (and 11 treated) patients were alive with a median overall survival of 46 months.

Conclusions

The administration of docetaxel via the hepatic artery is feasible. The highly interesting response and survival results observed in this limited series of patients warrant further studies.
Impact of Concurrent Radiotherapy on Chemotherapy Total Dose and Dose Intensity in Patients with Early Breast Cancer
Authors: Marenghi Cristina , Guglielmini Pamela , Verri Elena , Parodi Mariangela , Puntoni Matteo , Usset Antonella , Massoni Carola , Vormola Roberto , Boccardo Francesco
Published: July 2019

Aims and background

A retrospective analysis was conducted to evaluate the tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and radiation therapy on total CMF dose and dose intensity.

Methods

The medical records of 59 patients who had received conservative or radical surgery for breast cancer were analyzed. All patients had been assigned to 6 cycles of “1,8 CMF” adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and dose intensity were calculated. Toxicity was recorded scored according to WHO criteria.

Results

A total of 355 cycles was administered. Fifty of 59 patients received at least 85% of the programmed chemotherapy total dose, the median value being 100% (range, 42-100). The median relative dose intensity was 0.97 (range, 0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20 febrile neutropenia) and 29 (49%) required G-CSF support.

Conclusions

This retrospective analysis showed that it is possible to give concurrent CMF and breast radiation while ensuring adequate chemotherapy total doses and dose intensities to most patients. However, G-CSF support is required in a significant proportion of patients.
Long-Term Results in Patients Affected by Testicular Seminoma Treated with Radiotherapy: Risk of Second Malignancies
Authors: Fatigante Lucia , Ducci Francesco , Campoccia Silvana , Nocita Anna Morgana , Paci Enrico , Crocetti Emanuele , Cionini Luca
Published: July 2019

Aims

To report clinical results in patients with testicular seminoma treated with postoperative radiotherapy with regard to survival, acute and late toxicity, and risk of second malignancy.

Materials and methods

176 stage I-II testicular seminoma patients treated with radiotherapy from 1964 to 1994 at the Radiotherapy Division of Pisa University, using 60Co or Linac, were analyzed retrospectively. The follow-up ranged from 0.13 to 32.37 years, with a median of 12.1 years. The observed numbers of second malignancies were compared with those expected, taking into account age, sex, and incidence rates from the Tuscany Tumor Registry.

Results

Overall and specific survival at 10-15 years were 89-82% and 93-92%, respectively. Multivariate analysis revealed a significantly better survival in patients younger than 50 years and in those treated with Linac. Severe late sequelae occurred in 8% of the patients. Sixteen second malignancies were observed (14 solid tumors and 2 leukemias); median latency was 13 years (range, 3-27) and the observed/expected ratio 1.4 ( P not significant). Solid cancers were localized in the bladder (2), kidney (2), skin (2), stomach (1), prostate (1), lung (1), larynx (1), uvea (1) and contralateral testicle (1); 1 patient presented an intestinal carcinoid and 1 a metastasis from an unknown primary. The risk of a second malignancy was higher in the patient group receiving less than 4000 cGy (observed/expected, 2.8; P = 0.015).

Conclusions

The study confirmed the high cure rate in stage III seminomas after postoperative radiotherapy. Incidence of a second malignancy was higher than expected, but the difference was not statistically significant.
External Beam Radiotherapy in the Treatment of Male Breast Carcinoma: Patterns of Failure in a Single Institute Experience
Authors: Zabel Angelika , Milker-Zabel Stefanie , Zuna Ivan , Wannenmacher Michael , Debus Jürgen
Published: July 2019

Aims and background

We analyzed our own results in the treatment of male breast cancer patients with respect to local control, overall survival and possible prognostic factors for local and distant control.

Methods

Thirty-one patients with 32 carcinomas of the male breast were treated with radiotherapy. Twenty-five patients received radiotherapy to the chest wall including or not regional lymphatics after initial mastectomy (n = 23) or after surgery for local recurrence (n = 2). Median total dose was 60 Gy to the chest wall and 46 Gy to regional lymphatics. Seven patients with metastatic disease were referred for palliative radiotherapy.

Results

Overall survival after postoperative radiotherapy was 40% after a median follow-up of 4.3 years. Actuarial 3-, 5- and 10-year survival was 82.6%, 56.5% and 43.5%, respectively. Five-year progression-free survival was 62.5%. Survival was significantly affected by the presence of lymph node metastases ( P <0.001). Local recurrence was seen in one patient after 29 months.

Conclusions

Postoperative radiotherapy is important in the management of male breast cancer to improve local control and progression-free survival, resulting in one local failure in our analysis. The presence of lymph node metastases significantly impairs survival.
Italian Survey in Postoperative Radiation Therapy for Prostate Carcinoma by the Airo National Working Group on Prostate Radiotherapy: Definitive Results
Authors: Malinverni Giuseppe , Greco Carlo , Bianchi Pieromaria , Busutti Luciano , Cagna Emanuela , Cozzarini Cesare , Del Duca Massimo , Franzone Paola , Frezza Giovanni , Gabriele Pietro , Genovesi Domenico , Girelli Giuseppe Franco , Italia Corrado , Mandoliti Giovanni , Mauro Floranna , Nava Simonetta , Pratissoli Silvia , Saracino Maria Bianca , Squillace Luigi , Signor Marco , Tagliagambe Angiolo , Vavassori Vittorio , Villa Sergio , Zini Giampaolo , Valdagni Riccardo
Published: July 2019

Aims and background

The National Working Group on Prostate Radiotherapy of AIRO (Associazione Italiana Radioterapia Oncologica, Italian Association of Radiotherapeutic Oncology) was established in March 2001. A retrospective multicenter survey was performed to analyze the patterns of care for prostate cancer patients treated with postoperative radiotherapy following radical prostatectomy in Italy with regard to the year 2000.

Materials and methods

A structured questionnaire was mailed to 47 Italian radiotherapy centers to assess patient accrual in the postoperative setting in the interval comprised between period January-December 2000. Numbers of patients treated for different stages, specific prognostic factors indicating the need for adjuvant radiotherapy, fractionation schedules and prescription doses were acquired as well as other clinically important factors such as radiotherapy timing and the use of hormone therapy. More technical features of the treatment, such as patient positioning, mode of simulation, typical field setup and dose prescription criteria were also included in the questionnaire.

Results

The questionnaire was returned by 24 radiotherapy Institutions (51%) with a total number of 470 patients treated postoperatively in the year 2000. An average of about 20 patients were enrolled by each radiotherapy center. The age range was 45-81 years. Radiotherapy was delivered within 6 months of radical prostatectomy in 297 patients (65.4%) (mean, 3.4 months). In 157 (34.6%), the treatment was delivered as a salvage approach for biochemical or micro-macroscopic recurrence. Most of patients had locally advanced stage disease (pT3-pT4) (76%). Unfavorable prognostic factors, such as positive margins, capsular invasion, Gleason pattern score <7 were present in about 50% of patients.

Conclusions

The study confirmed that important risk factors for recurrences are present in a significant percentage of patients treated by radical prostatectomy. The number of patients that would benefit from adjuvant radiotherapy is therefore potentially very large. Future prospective studies should be conducted to assess and to clarify the respective roles of adjuvant and salvage radiotherapy in prostate cancer patients.
Results of Whole Brain Radiation Therapy in Patients with Brain Metastases from Colorectal Carcinoma
Authors: Amichetti Maurizio , Lay Giancarlo , Dessì Marina , Orrù Silvia , Farigu Roberta , Orrù Paola , Farci Daniele , Melis Sandro ,   Cagliari Neuro-Oncology Group, Battolu M , Bruder F , Cherchi C , Desogus A , Miragliotta G , Murtas S , Porcu G , Pusceddu C , Rais M , Sulas P
Published: July 2019

Aims and background

Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1-5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients.

Methods

Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes.

Results

Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis.

Conclusions

Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.
Human Papillomavirus Detection by Hybrid Capture II and Residual or Recurrent High-Grade Squamous Cervical Intraepithelial Neoplasia after Large Loop Excision of the Transformation Zone (LLETZ)
Authors: Sarian Luís Otávio , Derchain Sophie Françoise Mauricette , da Rocha Pitta Denise , Andrade Liliana Aparecida Angelo , Moráis Sirlei Siani , Figueiredo Priscila Garcia
Published: July 2019

Aims and background

The purpose of this study was to assess the association between highly-oncogenic types HPV DNA detection by Hybrid Capture II (HCII) and residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2 or 3) during the follow-up of women submitted to large loop excision of the transformation zone (LLETZ).

Study design

In this cohort study, 94 women submitted to LLETZ because of CIN 2 or 3 between March 2001 and September 2002 were followed up twice yearly until September 2003. Follow-up visits consisted of an interview regarding clinical, social and demographic characteristics complemented with gynecological examination with specimen collection for Pap test and HCII and colposcopy. Eighty-one patients attended the first visit (mean 4.8 months, range 3-6) and 75 the second visit (mean 10.9 months, range 7-17 months). McNemar's test to assess the variation of HPV DNA detection following LLETZ, odds ratios (OR) to evaluate the correlation between HPV DNA positivity and residual/recurrent CIN during follow-up, and logistic regression to assess the risk of residual/recurrent CIN were used.

Results

There was a strong and significant reduction in HPV detection after LLETZ ( P <0.001). HPV DNA detection was correlated with residual/recurrent CIN at the first (OR = 103.4; 95% CI 5.5 to 1961.2) and second (OR = 12.7; 95% CI 1.1 to 345.5) follow-up visits. Multivariate analysis showed HPV persistence as a stand-alone risk factor for residual/recurrent CIN (OR = 50.3; 95% CI 3.8 to 663.1).

Conclusions

High risk HPV DNA detection decreased substantially after CIN treatment with LLETZ, but HPV persistence was strongly correlated with residual/recurrent CIN.
A Short Impact of Epidemiological Features of Colorectal Cancer in Iran
Authors: Pahlavan Payam Samareh , Jensen Katrin
Published: July 2019

Aims and background

The incidence of colorectal cancer varies from one country to another although the variation is not much different in neighboring countries. Even in one country there is no relevant variation in incidence from one province to another. A study of different provinces in a vast developing country, Iran, was performed to determine the incidence of colorectal cancer.

Methods

Information from cancer registries of four provinces in the north, north-west and central-south of Iran regarding colorectal cancer was gathered for analysis. A total of 1628 cases with colorectal cancer in a total population of 6,435,549 was identified.

Results and conclusions

In all provinces, there were more male than female patients with colorectal cancer. The study also showed that the incidence of the disease in young patients was higher than expected. Except for Israel because of genetic factors, these provinces showed one of the highest ASR among Asian countries. This finding probably indicates more westernization in the Iranian diet with a genetic influence. Some social habits including dietary and tobacco smoking may also influence the incidence of colorectal cancer in the Iranian population. Community-related risk factors need further investigation, especially in the high-risk Northern part of the country.
Vacuum-Assisted Core Biopsy (Mammotome) for the Diagnosis of Non-Palpable Breast Lesions: Four-Year Experience in an Italian Center
Authors: Costantini Raffaele , Sardellone Augusto , Marino Cristiana , Giamberardino Maria Adele , Innocenti Paolo , Napolitano Antonio Maria
Published: July 2019

Aims and background

Microinvasive biopsy techniques are increasingly employed in the diagnostic assessment of non-palpable breast lesions (NPBLs). This study reports the four-year experience of an Italian surgical center in the evaluation of the diagnostic effectiveness versus adverse effects of vacuum-assisted core biopsy (Mammotome).

Methods

314 NPBLs with a dubious ultrasound and/or radiographic appearance were subjected to mammography-guided (86) or ultrasound-guided (228) Mammotome biopsy.

Results

The procedure could be completed and was diagnostic in 305 cases (P <0.0001). Adverse events were transient lightheadedness. in two cases and moderate bleeding in three cases. Histological processing of the biopsies showed 227 cases of benign disease (74.42%), 68 cases of carcinoma (20 carcinomas in situ and 48 infiltrating carcinomas) (22.29%), nine cases of atypical ductal hyperplasia (2.95%) and one atypical lobular hyperplasia (0.33%). Only 12 patients reported mild discomfort relative to the procedure. The difference between the number of patients reporting discomfort and that of patients reporting no discomfort at all was highly significant (P <0.0001).

Conclusions

The results confirm that Mammotome biopsy is a highly effective procedure for the diagnosis of NPBLs, with minimal negative effects.