Future Oncology Ahead of Print.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 9 Ιουνίου 2016
The applications of the novel polymeric fluoropyrimidine F10 in cancer treatment: current evidence
Trials Produce Practice-Changing Results for Brain Cancer
The standard treatment that some patients with brain cancer receive is likely to change, based on findings from two large clinical trials presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago this week.
Both trials showed that administering the chemotherapy drug temozolomide (Temodar®) in addition to radiation therapy increased how long patients lived overall and without their disease progressing. The trial investigators and other leading brain cancer researchers agreed that the results of the two trials will change the standard of care.
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Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors
Abstract
Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95%CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95%CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95%CI 1.26-6.11; and 1965-1974: PR 1.55, 95%CI 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades. This article is protected by copyright. All rights reserved.
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Patterns of recurrence and treatment in male breast cancer: A clue to prognosis?
Abstract
Introduction: Male breast cancer(MBC) patients seem to have inferior survival compared to female(FBC) ones, which is not fully explained by usual prognostic factors. Recurrence analysis could show differences in relapse patterns and/or in patients' approaches that justify these outcomes.
Material/Methods: Retrospective analysis of MBC patients treated in a cancer center between 1990-2014, looking for relapse. For each patient, three matched FBC patients were selected by: diagnosis' year, age (within 5 years), stage and tumors' type (only luminal-like were considered). Differences between cohorts were assessed by χ2 test and hierarchical clustering was performed to define subgroups according to relapse local. Survival curves were calculated by Kaplan-Meier and compared using log-rank test. Statistical significance was defined as p<0.05.
Results: Groups were balanced according to age, histological grade, stage, expression of hormonal receptors and adjuvant treatments. Median time to recurrence was equivalent, p=0.72, with the majority of patients presented with distant metastases, p=0.69, with more lung involvement in male, p=0.003. Male patients were more often proposed to symptomatic treatment (21.1% vs 4.4%, p=0.02). Overall and from recurrence survivals were poorer for male, median: 5years (95%CI:4.1-5.9 years) and 1year (95%CI:0-2.1 years) vs 10years (95%CI:7.8-12.2 years) and 2years (95%CI:1.6-2.4 years), p<0.001 and p=0.004, respectively, and this tendency remained in the five cluster subgroups, that identified five patterns of relapse, p=0.003.
Discussion: MBC patients had the worst survival, even after controlling important factors, namely the local of relapse. Palliative systemic treatment had favorable impact in prognosis and its frequently avoidance in male could justify the outcomes differences. This article is protected by copyright. All rights reserved.
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Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling
Abstract
Pancreatic adenocarcinoma (PDAC) is known to have a poor prognosis partly because of lack of effective biomarkers. In the test set, we investigated dysbindin (DTNBP1) as a potential biomarker for PDAC by comparing preoperative and postoperative serum mass spectrometry (MS) proteomic profilings. Of the included 50 PDAC patients, 42 (positivity of 84.0%) detected a lower MS peak in postoperative serums than preoperative ones which was then identified as dysbindin.In the verification set, receiver operating characteristics (ROC) were used to assess diagnostic efficiency. 550 participants were included in the verification set (250 with PDAC, 80 with benign biliary obstruction [BBO], 70 with chronic pancreatitis [CP] and 150 healthy donors [HD]). Dysbindin was increased in PDAC patient sera than in all controls. ROC curves revealed the optimum diagnostic cutoff for dysbindin was 699.16 pg/ml (area under curve [AUC] 0.849 [95% CI 0.812-0.885], sensitivity 81.9% and specificity 84.7%). Raised concentration of dysbindin in sera could differentiate PDAC from BBO, CP and HD. Moreover, dysbindin maintained its diagnostic accuracy for PDAC patients who were CA19-9 negative (AUC 0.875 [95%CI 0.804-0.945], sensitivity 83.0%, specificity 89.0%) and for patients with benign biliary obstruction (AUC 0.849 [95%CI 0.803-0.894], sensitivity 82.3%, specificity 84.0%).Our discovery of dysbindin may complement measurement of CA19-9 in the diagnosis of PDAC and help to discriminate PDAC from other pancreatic diseases or begin biliary obstruction. This article is protected by copyright. All rights reserved.
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Curcumin: A new candidate for melanoma therapy?
Abstract
Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic, and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g. BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin. This article is protected by copyright. All rights reserved.
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Use of endocrinological and neurological medication among 5-year survivors of young onset brain tumors
Abstract
The burden of late-effects for young onset brain tumor (BT) survivors needs more careful evaluation. Our aim was to assess the need for endocrinological and neurological medication among this specific group. We identified 5-year survivors diagnosed at the age of 0–24 years between 1988 and 2004 from the Finnish Cancer Registry (N = 602). Data on endocrinological and neurological drug purchases were collected from the Social Insurance Institution of Finland. Five years after diagnosis the most commonly purchased drugs had been: antiepileptics (44.8 %), systemic hydrocortisone (18.3 %), female sex hormones (17.6 %), thyroid hormones (11.2 %), and growth hormone (10.0 %). The survivors showed an increased hazard ratio (HR) for a need for new types of drugs still 5 years after diagnosis. Thyroid hormones (HR 10.6, 95 % CI 5.1–21.4), estrogens (HR 8.0, 95 % CI 2.1–25.7), and antiepileptics (HR 6.3, 95 % CI 3.4–11.2) were bought with high frequencies. Irradiation increased the hazard for drug-purchases other than antiepileptics. Cumulative incidence of purchases of estrogens or androgens increased still 15 years after diagnosis. The cumulative incidence of purchasing thyroid hormones and antiepileptics showed continuous increase for the youngest group, whereas survivors diagnosed at 15–24 years of age reached stable level before 15 years from diagnosis. The need for new medication continued more than a decade after BT diagnosis. Especially the need for new thyroid or sex hormone medication among childhood BT survivors may emerge long after diagnosis.
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Brainstem gangliogliomas: prognostic factors, surgical indications and functional outcomes
Abstract
To explore the prognostic factors and discuss the surgical indications of brainstem gangliogliomas. Twenty-one patients with brainstem ganglioglioma were surgically treated at our hospital between 2006 and 2014. The clinical, radiological, operative, and pathological findings of these patients were retrospectively reviewed. The 3-years overall survival and event-free survival (EFS) rates were 90.5 % and 68.4 %, respectively. Four patients (4/18, 22 %) experienced a recurrence with a mean recurrence-free survival of 5.5 months and a mean follow-up of 37 months. Three patients died of surgery-related complications. Three growth patterns were identified: exophytic (6/21), intrinsic (2/21), and endo-exophytic (13/21). Eight patients (8/15, 53 %) harbored a BRAF V600E mutation. All recurrent tumors were endo-exophytic, and except the one without molecular information, were BRAF V600E mutants. A Cox hazard proportion ratio model was used to identify factors influencing EFS, including sex, age, location, growth patterns, extent of resection (EOR), and BRAF V600E mutation status. On univariate analysis, none of these factors reached statistical significance. Among them, EOR and growth patterns were strongly associated with each other (Fisher's exact test, P < 0.01). A multivariate analysis demonstrated that growth patterns were the only factor associated with EFS (P = 0.02; HR 49.05; 95 % CI 1.76–1365.13). Growth patterns may be useful to select surgery candidates and predict prognosis for patients with brainstem gangliogliomas. BRAF V600E was frequently present and appeared to be associated with shorter recurrence-free survival. Studies on BRAF V600E-targeted therapy for patients with high surgical risks are needed.
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Conditional survival after diagnosis with malignant brain and central nervous system tumor in the United States, 1995–2012
Abstract
General population-based survival statistics for primary malignant brain or other central nervous system (CNS) tumors do not provide accurate estimations of prognosis for individuals who have survived for a significant period of time. For these persons, the use of conditional survival percentages provides more accurate information to estimate potential outcomes. Using information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program from 1995 to 2012, conditional survival percentages were calculated for 1 or 5 years of additional survival for all primary malignant brain and CNS tumors overall and by gender, race, ethnicity and age. Rates were calculated to include 1, 2, 3, 4, 5, 10 and 15 years post diagnosis. Conditional survival was also calculated in intervals from 1995–2004 to 2005–2012, to examine the potential effect that the introduction of new treatment protocols may have had on survival rates. The percentage of patients surviving one or five additional years varied by histology, age at diagnosis, gender, race and ethnicity. Younger persons (age <15 years at diagnosis) had higher conditional survival percentages for all histologies as compared to all histologies in older patients (age ≥15 years at diagnosis). The longer the amount of time post-diagnosis of a malignant brain or other CNS tumor, the higher the conditional survival. Younger persons at diagnosis had the highest conditional survival irrespective of histology. Use of conditional survival rates provides relevant additional information for patients and their families, as well as for clinicians and researchers, and helps with understanding prognosis.
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Brain regions associated with telomerase reverse transcriptase promoter mutations in primary glioblastomas
Abstract
Human telomerase reverse transcriptase (TERT) promoter mutations are important genetic alterations in many kinds of human malignancies, including glioma. The current study aimed to investigate the anatomical specificity of TERT promoter mutations in glioblastomas (GBMs). Clinical information and preoperative magnetic resonance images of 203 patients with GBMs were reviewed. TERT promoter mutation status was assessed by Sanger sequencing in all cases. Tumor lesions were manually segmented and then registered to a standard brain atlas. Then the specific brain regions associated with TERT promoter mutation status were subsequently identified by voxel-based regression analysis. TERT promoter mutations were detected in 94 (46.3 %) of the 203 patients. Voxel-based statistical analysis demonstrated that GBMs with TERT promoter mutations were much more likely to locate in the right temporal lobe, while those with wild-type TERT promoters were more likely to occur in the anterior region of the right lateral ventricle. No significant difference was found in the lesion volumes of the T2-identified tumor or in the contrast enhancement areas between the two groups. The current study demonstrated the anatomic specificity of TERT promoter mutation status in GBM. These findings may provide new insight into the molecular classification of GBM and further our understanding of the associations between tumor-specific molecular alterations and tumor location.
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Exploratory study of the effect of brain tumors on the default mode network
Abstract
Resting state functional magnetic resonance imaging (RS-fMRI) is a popular method of visualizing functional networks in the brain. One of these networks, the default mode network (DMN), has exhibited altered connectivity in a variety of pathological states, including brain tumors. However, very few studies have attempted to link the effect of tumor localization, type and size on DMN connectivity. We collected RS-fMRI data in 73 patients with various brain tumors and attempted to characterize the different effects these tumors had on DMN connectivity based on their location, type and size. This was done by comparing the tumor patients with healthy controls using independent component analysis (ICA) and seed based analysis. We also used a multi-seed approach described in the paper to account for anatomy distortion in the tumor patients. We found that tumors in the left hemisphere had the largest effect on DMN connectivity regardless of their size and type, while this effect was not observed for right hemispheric tumors. Tumors in the cerebellum also had statistically significant effects on DMN connectivity. These results suggest that DMN connectivity in the left side of the brain may be more fragile to insults by lesions.
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Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats
Abstract
Glioblastomas (GBMs) are aggressive brain tumours with a dismal prognosis, despite combined surgery, radio- and chemotherapy. Close to 90 % of all GBMs harbour a deregulated PI3K pathway, which is essential in regulating central cellular functions such as proliferation, cell growth, motility and survival. Thus, PI3K represents a potential target for molecular therapy in GBM. We investigated the anti-tumour efficacy of the PI3K inhibitor buparlisib (NVP-BKM120) in GBM cell lines in vitro and in vivo, when treatment was initiated after MRI-confirmed tumour engraftment. We found that buparlisib inhibited glioma cell proliferation in a dose dependent manner, demonstrated by MTS assay, manual cell count and BrdU incorporation. A dose dependent increase in apoptosis was observed through flow cytometric analysis. Furthermore, by immunocytochemistry and western blot, we found a dose dependent inhibition of Akt phosphorylation. Moreover, buparlisib prolonged survival of nude rats harboring human GBM xenografts in three independent studies and reduced the tumours' volumetric increase, as determined by MRI. In addition, histological analyses of xenograft rat brains showed necrotic areas and change in tumour cell nuclei in buparlisib-treated animals. The rats receiving buparlisib maintained their weight, activity level and food- and water intake. In conclusion, buparlisib effectively inhibits glioma cell proliferation in vitro and growth of human GBM xenografts in nude rats. Moreover, the compound is well tolerated when administered at doses providing anti-tumour efficacy. Thus, buparlisib may have a future role in glioma therapy, and further studies are warranted to validate this compound for human use.
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Molecular evaluation of PIK3CA gene mutation in breast cancer: determination of frequency, distribution pattern and its association with clinicopathological findings in Indian patients
Abstract
Somatic mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful marker for prognosis and therapeutic target. Activating mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in 18–40 % of breast carcinomas. In this study, we evaluated PIK3CA mutation in 185 Indian breast cancer patients by direct DNA sequencing. PIK3CA mutations were observed in 23.2 % (43/185) of breast tumor samples. PIK3CA mutations were more frequent exon 30 (76.8 %) than in exon 9 (23.2 %). Mutations were mostly clustered within two hotspot region between nucleotides 1624 and 1636 or between 3129 and 3140. Sequencing analysis revealed four different missense mutations at codon 542 and 545 (E542K, E545K, E545A and E545G) in the helical domain and two different amino acid substitutions at codon 1047 (H1047R and H1047L) in the kinase domain. None of the cases harbored concomitant mutations at multiple codons. PIK3CA mutations were more frequent in older patients, smaller size tumors, ductal carcinomas, grade II tumors, lymph node-positive tumors and non-DCIS tumors; however, none of the differences were significant. In addition, PIK3CA mutations were common in ER+, PR+ and HER2+ cases (30 %), and a comparatively low frequency were noted in triple-negative tumors (13.6 %). In conclusion, to our knowledge, this is the largest study to evaluate the PIK3CA mutation in Indian breast cancer patients. The frequency and distribution pattern of PIK3CA mutations is similar to global reports. Furthermore, identification of molecular markers has unique strengths and can provide insights into the pathogenic process of breast carcinomas.
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"Anticancer Res"[jour]; +103 new citations
103 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2016/06/09
PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Searching for certainty: findings predictive of appendicitis in equivocal ultrasound exams
Abstract
Background
Ultrasound (US) is the preferred imaging modality for evaluating suspected pediatric appendicitis. However, borderline appendiceal enlargement or questionable inflammatory changes can confound interpretation and lead to equivocal exams.
Objective
The purpose of this study was to determine which findings on equivocal US exams are most predictive of appendicitis.
Materials and methods
All US exams performed for suspected pediatric appendicitis from July 1, 2013, through July 9, 2014, were initially interpreted using a risk-stratified scoring system. Two blinded pediatric radiologists independently reviewed US exams designated as equivocal and recorded the following findings: increased wall thickness, loss of mural stratification, peri-appendiceal fat inflammation, peri-appendiceal fluid, appendicolith and maximum appendiceal diameter. A third pediatric radiologist resolved discrepancies. US features were correlated with the final diagnosis via multivariate analysis.
Results
During the study period, 162/3,750 (4.3%) children had US exams initially interpreted as equivocal (mean age 9.8 +/- 3.8 years). Five outpatients were lost to follow-up. Forty-eight of the remaining 157 (30.6%) children had an operative diagnosis of appendicitis. Findings significantly associated with appendicitis were loss of mural stratification (odds ratio [OR] = 6.7, P=0.035), peri-appendiceal fat inflammation (OR = 10.0, P<0.0001) and appendicolith (OR = 15.8, P=0.025). While appendiceal diameter tended to be larger in patients with appendicitis, the difference was not statistically significant.
Conclusion
Loss of mural stratification, peri-appendiceal fat inflammation and an appendicolith are significant predictors of appendicitis in children with otherwise equivocal US exams. While maximum appendiceal diameter is not statistically associated with appendicitis in our study, mean appendiceal diameter of 6.7 mm in those without appendicitis suggests that the customary upper normal limit of 6 mm is too sensitive.
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Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams
Abstract
Background
Recent reports have suggested residual gadolinium deposition in the brain in subjects undergoing multiple contrast-enhanced MRI exams. These findings have raised some concerns regarding gadolinium-based contrast agent (GBCA) usage and retention in brain tissues.
Objective
To summarize findings of hyperintense brain structures on precontrast T1-weighted images in 21 children undergoing multiple GBCA MRI exams.
Materials and methods
This retrospective study involved 21 patients, each of whom received multiple MRI examinations (range: 5-37 exams) with GBCA over the course of their medical treatment (duration from first to most recent exam: 1.2-12.9 years). The patients were between 0.9 and 14.4 years of age at the time of their first GBCA exam. Regions of interest were drawn in the dentate nucleus and the globus pallidus on 2-D fast spin echo images acquired at 1.5 T. The signal intensities of these two structures were normalized by that of the corpus callosum genu. Signal intensity ratios from these patients were compared to control patients of similar ages who have never received GBCA.
Results
Signal intensity ratios increased between the first and the most recent MRI exam in all 21 patients receiving GBCA, with an increase of 18.6%±12.7% (range: 0.5% to 47.5%) for the dentate nucleus and 12.4%±7.4% (range: -1.2% to 33.7%) for the globus pallidus (P<0.0001). Signal intensity ratios were also higher in GBCA patients than in controls (P<0.01). The degree of signal intensity enhancement did not correlate with statistical significance to the cumulative number or volume of GBCA administrations each patient received, the patient's age or the elapsed time between the first and most recent GBCA MRI exams.
Conclusion
These results in children are consistent with recent findings in adults, suggesting possible gadolinium deposition in the brain.
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"Asian Pac J Cancer Prev"[jour]; +66 new citations
66 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"Asian Pac J Cancer Prev"[jour]
These pubmed results were generated on 2016/06/09
PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology
Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.
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Integrating Palliative Care in Pediatric Oncology: Evidence for an Evolving Paradigm for Comprehensive Cancer Care
Background: The demonstrated benefit of integrating palliative care (PC) into cancer treatment has triggered an increased need for PC services. The trajectory of integrating PC in comprehensive cancer centers, particularly pediatric centers, is unknown. We describe our 8-year experience of initiating and establishing PC with the Quality of Life Service (QoLS) at St. Jude Children's Research Hospital. Methods: We retrospectively reviewed records of patients seen by the QoLS (n=615) from March 2007 to December 2014. Variables analyzed for each year, using descriptive statistics, included diagnostic groups, QoLS encounters, goals of care, duration of survival, and location of death. Results: Total QoLS patient encounters increased from 58 (2007) to 1,297 (2014), new consults increased from 17 (2007) to 115 (2014), and mean encounters per patient increased from 5.06 (2007) to 16.11 (2014). Goal of care at initial consultation shifted from primarily comfort to an increasing goal of cure. The median number of days from initial consult to death increased from 52 days (2008) to 223 days (2014). A trend toward increased outpatient location of death was noted with 42% outpatient deaths in 2007, increasing to a majority in each subsequent year (range, 51%–74%). Hospital-wide, patients receiving PC services before death increased from approximately 50% to nearly 100%. Conclusions: Since its inception, the QoLS experienced a dramatic increase in referrals and encounters per patient, increased use by all clinical services, a trend toward earlier consultation and longer term follow-up, increasing outpatient location of death, and near-universal PC involvement at the end-of-life. The successful integration of PC in a comprehensive cancer center, and the resulting potential for improved care provision over time, can serve as a model for other programs on a broad scale.
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The Relevance of Hereditary Cancer Risks to Precision Oncology: What Should Providers Consider When Conducting Tumor Genomic Profiling?
Through tumor genomic profiling (TGP), existing and novel treatments can be selected to better target the specific dysregulated molecular pathways that drive growth and spread of a patient's tumor. Although the primary purpose of TGP is to detect targetable somatic mutations for treatment, TGP may also uncover germline mutations with important implications for patients and family members. Oncology care providers should be aware of the hereditary cancer risks associated with genes commonly tested by TGP. Further, patients should be informed about the possible discovery of hereditary cancer risk information and the relevance of this information to their health and that of family members, and should have their preferences toward further evaluation of hereditary risk information that could be revealed by TGP documented in the medical record and followed.
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Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites
Background: The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites. Methods: Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS). Results: A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13–12.79) was significantly greater than the target grade level of 6 (middle-school: P<.001). No difference between comprehensive and noncomprehensive centers was identified. Regional differences were identified in 4 of the 10 readability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01). Conclusions: OPI from NCIDCC Web sites is more complex than recommended for the average patient.
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Cytogenetic Evolution Associated With Disease Progression in Hematopoietic Neoplasms With t(8;22)(p11;q11)/BCR-FGFR1 Rearrangement
Hematopoietic neoplasms with FGFR1 rearrangements are rare. Clinically, patients often present with a chronic myeloproliferative neoplasm with eosinophilia and an increased risk of transformation to acute leukemia. We report a patient who initially presented with B-cell acute lymphoblastic leukemia (B-ALL) with t(8;22)(p11.2;q11.2) and an additional derivative chromosome 22 [der(22)t(8;22)]. After induction chemotherapy, B-ALL blasts were eradicated; however, a chronic myeloproliferative process emerged showing persistent t(8;22) (p11.2;q11.2) but not der(22)t(8;22). Combined morphologic and fluorescence in situ hybridization revealed that both lymphoblasts and myeloid cells harbored t(8;22)(p11.2;q11.2); but only lymphoblasts carried the additional der(22)t(8;22). This case provides direct evidence to illustrate the clonal relationship of chronic phase and blast phase in myeloid neoplasms with FGFR1 rearrangement, and demonstrates that clonal cytogenetic evolution plays an important role in disease progression.
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Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo
Abstract
Ovarian cancer is the leading cause of death among gynecological malignancies, and high grade serous ovarian carcinoma is the most common and most aggressive subtype. Recently, it was demonstrated that cAMP mediates protein kinase A-independent effects through Epac (exchange protein directly activated by cAMP) proteins. Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular calcium handling and formation of cell–cell junctions. Several reports document that Epac1 could play vital roles in promoting proliferation, invasion and migration of some cancer cells. However, the expression levels and roles of Epac1 in ovarian cancer have not been investigated. In the present study, we detected the expression levels of Epac1 mRNA and protein in three kinds of ovarian cancer cells SKOV3, OVCAR3 and CAOV3. Furthermore, the effect of Epac1 knockdown on the proliferation and apoptosis of SKOV3 and OVCAR3 cells was evaluated in vitro and in vivo. The results showed that there was higher expression of Epac1 mRNA and protein in SKOV3 and OVCAR3 cells. Epac1 knockdown inhibited the proliferation of SKOV3 and OVCAR3 cells in vitro and in vivo. Decreased proliferation may be due to downregulation of Epac1-induced G1 phase arrest by inactivating the AKT/Cyclin D1/CDK4 pathway, but not to alterations in the MAPK pathway or to apoptosis. Taken together, our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer.
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CTCs and cfDNA in NSCLC patients treated with erlotinib
Background: Genotype-directed therapy is standard-of-care for advanced NSCLC, but obtaining tumor tissue for genotyping remains a challenge. CTC or cfDNA analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression. Methods: EGFR-mutant NSCLC patients were enrolled in a phase II trial of erlotinib. Blood was collected at baseline, every 2 months on study, and at disease progression. Plasma genotyping was performed by droplet digital PCR for EGFR19del, L858R, and T790M. CTCs were isolated by CellSave, enumerated, and analyzed by immunofluorescence for CD45 and pan-cytokeratin and EGFR and MET FISH were. Rebiopsy was performed at disease progression. Results: 60 patients were enrolled; 44 patients discontinued therapy for disease progression. Rebiopsy ocurred in 35/44 patients (80%), with paired CTC/cfDNA analysis in 41/44 samples at baseline and 36/44 samples at progression. T790M was identified in 23/35 (66%) of tissue biopsies and 9/39 (23%) of cfDNA samples. CTC analysis at progression identified MET amplification in 3 samples in which tissue analysis could not be performed. cfDNA analysis identified T790M in 2 samples in which rebiopsy was not possible. At diagnosis, high levels of cfDNA but not high levels of CTCs correlated with progression-free survival.. Conclusions: cfDNA and CTCs are complementary, noninvasive assays for evaluation of acquired resistance to first-line EGFR TKIs and may expand the number of patients in whom actionable genetic information can be obtained at acquired resistance. Serial cfDNA monitoring may offer greater clinical utility than serial monitoring of CTCs.
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Clinical implications of crizotinib pharmacokinetics
Purpose:We assessed the effect of baseline patient demographic and disease characteristics on the crizotinib pharmacokinetic parameters oral clearance (CL/F), volume of distribution (V2/F), and area-under-the-curve at steady state (AUCss) following multiple crizotinib 250-mg twice-daily dosing in patients with ALK-positive cancer. Experimental Design:A pharmacokinetic model was fit to data from 1,214 patients. We identified statistically significant covariates (P{less than or equal to}0.001) by evaluating their effects on CL/F and V2/F and estimated their magnitudes. Results:Age, Eastern Cooperative Oncology Group performance status, aspartate aminotransferase (AST) levels, albumin levels, and smoking status had no effect on CL/F or V2/F. Statistically significant covariates were Asian race and female sex for CL/F and V2/F and body weight, creatinine clearance (CLcr), and total bilirubin for CL/F only. The model predicted that CL/F would be 9% lower or higher in a 40-kg or a 100-kg patient, respectively; 16% lower in patients with CLcr 30 mL/min; 23% lower in Asians; and 11% lower in females than the reference patient (65-kg non-Asian male; baseline CLcr, 91.6 mL/min; total bilirubin, 0.41 mg/dL). The effect of total bilirubin on CL/F was small. V2/F was 23% lower in Asians than non-Asians and females than males. Effects of all significant covariates on AUCss were not predicted to be clinically relevant. Conclusions:Crizotinib at a 250-mg twice-daily starting dose appears to be appropriate for all patients irrespective of age, sex, race, body weight, mild or moderate renal impairment, or hepatic function (in the range evaluated: bilirubin {less than or equal to}2.1 mg/dL or AST {less than or equal to}124 U/L).
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Targeting SOAT1 to treat glioblastoma
Purpose: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is a novel characteristic of glioblastoma (GBM). The aim of this study was to identify effective approaches to suppress GBM growth by inhibition of SREBP-1. As SREBP activation is negatively regulated by endoplasmic reticulum (ER) cholesterol, we sought to determine whether suppression of sterol O-acyltransferase (SOAT), a key enzyme converting ER cholesterol to cholesterol esters (CE) to store in lipid droplets (LDs), effectively suppressed SREBP-1 and blocked GBM growth. Experimental Design: The presence of LDs in glioma patient tumor tissues was analyzed using immunofluorescence, immunohistochemistry and electronic microscopy. Western blotting and real-time PCR were performed to analyze protein levels and gene expression of GBM cells, respectively. Intracranial GBM xenografts were used to determine the effects of genetically silencing SOAT1 and SREBP on tumor growth. Results: Our study unraveled that cholesterol esterification and LD formation are signature of GBM, and human patients with glioma possess elevated LDs that correlate with GBM progression and poor survival. We revealed that SOAT1 is highly expressed in GBM and functions as a key player in controlling the cholesterol esterification and storage in GBM. Targeting SOAT1 suppresses GBM growth and prolongs survival in xenograft models via inhibition of SREBP-1-regulated lipid synthesis. Conclusions: Cholesterol esterification and storage in LDs are novel characteristics of GBM, and inhibiting SOAT1 to block cholesterol esterification is a promising therapeutic strategy to treat GBM by suppressing SREBP-1.
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Gonadotropin-releasing hormone agonist-induced pituitary apoplexy
Summary
Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour.
Learning pointsWhile non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare.
Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas.
GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma.
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Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2
Abstract
Purpose
In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16–20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment.
Materials and methods
All sequential treatment naïve mRCC patients treated with HDIL-2 at the University of Utah (1988–2013) and University of Michigan (1997–2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months.
Results
391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48–1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39–1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09–0.22, p < 0.0001) and overall survival (HR 0.33, 95 % CI 0.23–0.48, p < 0.0001) were observed between patients achieving stable disease compared to those with progressive disease and who were not evaluable.
Conclusions
Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses.
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Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
Abstract
Background
Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.
Methods
We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.
Results
The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93–11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.
Conclusion
The present study provides further evidence for a role of P. acnes in prostate cancer development.
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Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2
Abstract
Purpose
In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16–20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment.
Materials and methods
All sequential treatment naïve mRCC patients treated with HDIL-2 at the University of Utah (1988–2013) and University of Michigan (1997–2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months.
Results
391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48–1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39–1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09–0.22, p < 0.0001) and overall survival (HR 0.33, 95 % CI 0.23–0.48, p < 0.0001) were observed between patients achieving stable disease compared to those with progressive disease and who were not evaluable.
Conclusions
Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses.
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Gonadotropin-releasing hormone agonist-induced pituitary apoplexy
Summary
Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour.
Learning pointsWhile non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare.
Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas.
GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma.
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Spirituality, Emotional distress, and post-traumatic Growth in breast cancer survivors and their partners: An actor–partner interdependence modeling approach
Abstract
Background
The association between spirituality and emotional health has been well documented in healthy individuals. A small literature has shown that spirituality plays a role in well-being for some breast cancer survivors (BC survivors), however this link is virtually unexplored in partners/spouses of survivors. The current study aimed to assess the relationship between spirituality, emotional distress, and post-traumatic growth for BC survivors and their partners using a dyadic analyses approach.
Methods
498 couples who were 3-8 years post breast cancer diagnosis were recruited from the Eastern Oncology Group database.
Results
For BC survivors and their partners, greater levels of spirituality were associated with increases in their own post-traumatic growth. There was no relation between BC and partner spirituality and their own emotional distress, but partner's spirituality was associated with reduced occurrence of intrusive thoughts in the BC survivor. In contrast, BC survivors' spirituality was found to be wholly unrelated to partner's mental health and adjustment.
Conclusions
Following diagnosis and treatment, spirituality appears to associate with positive growth in BC survivors and their partners. However, BC survivor and partner spirituality seem to be ineffective at impacting the other's post-traumatic growth or emotional distress, with the exception of intrusive thoughts. Dyadic analysis takes into account the reciprocal influence of close relationships on health, and is an important and under-utilized methodology in behavioral oncology research and clinical practice.
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Perceptions of cancer treatment decision making among american indians/alaska natives and their physicians
Abstract
Objective
American Indian/Alaska Native (AI/AN) patients are significantly less likely than non-Hispanic whites to receive guideline-concordant cancer care. Our objective was to examine cancer treatment decision making among AI/AN patients and their providers.
Methods
From 2011-14, AI/AN cancer patients and their surgeons were identified through a hospital registry in Washington State. Patients were invited to participate in a mailed survey that queried socio-demographics, cultural affiliation, everyday perceived discrimination, and trust in providers. Both patients and surgeons were queried about decision-making quality (collaboration and satisfaction). The primary outcome was association between patient and provider assessments of decision-making quality. The secondary outcome was non-adherence to treatment.
Results
49 patients (62% response rate) and 14 surgeons (37% response rate) returned surveys. Half of patients had not completed high school; 41% were living in poverty. Half of patients reported a strong tribal affiliation and most reported experiencing some form of discrimination. Patients endorsed high trust in surgeons and a high quality decision-making process; and surgeons' rated decision-making quality even more highly than patients did in every domain. Non-adherence to treatment recommendations was common (26%) and was significantly associated with lower patient-reported collaboration and satisfaction with decision making.
Conclusions
Given the importance of adherence to cancer treatment for survival, the many non-clinical reasons for non-adherence, and the currently demonstrated association between decision-making quality and adherence, it would be worthwhile to investigate how to increase AI/AN patient satisfaction with decision making and whether improving satisfaction yields improved adherence to the cancer treatment plan.
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Objective-subjective disparity in cancer-related cognitive impairment: does the use of change measures help reconcile the difference?
Abstract
Objective
Studies to date have found little correlation between subjective and objective measures of cognitive function in cancer patients, making it difficult to interpret the significance of their cognitive complaints. The purpose of this study was to determine if a stronger correlation would be obtained using measures of cognitive change rather than static scores.
Methods
Sixty women with early stage breast cancer underwent repeated cognitive assessment over the course of chemotherapy with a neuropsychological test battery (objective measure) and with the FACT-Cog (subjective measure). Their results were compared to 60 healthy women matched on age and education and assessed at similar intervals. We used multilevel modeling, with FACT-Cog as the dependent measure and ordinary least squares slopes of a neuropsychological summary score as the independent variable, to evaluate the co-variation between the subjective and objective measures over time
Results
Measures of both objective and subjective cognitive function declined over the course of chemotherapy in the breast cancer patients but there was no significant relationship between them, even when using change measures. Change in objective cognitive function was not related to change in anxiety or fatigue scores but the decline in perceived cognitive function was associated with greater anxiety and fatigue.
Conclusions
The discrepancy in objective and subjective measures of cognition in breast cancer patients cannot be accounted for in terms of a failure to use change measures. Although the results are negative, we contend that this is the more appropriate methodology for analyzing cancer-related changes in cognition.
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Use of Combined PMMC and Nasolabial Flap for Reconstruction of Full Thickness Cheek Defect Involving Lip Commisure
Abstract
Head neck cancer constitute significant cancer burden and among it carcinoma of oral cavity involving buccal mucosa is most common entity in India. Very often it involves lip commisure. Radical surgery along with radiotherapy still remains treatment of choice. Reconstruction of composite defect of oral cavity fallowing ablative surgery remains difficult task. Reconstruction of lip commisure defect after primary tumor excision is still a big challenge. Micro vascular technique primary repair is main modality of treatment which needs great surgical expertise in plastic surgery which is not possible in every institution. We propose a novel surgical reconstructive technique of use of combine pectoralis major myocutaneous flap (PMMC) with nasolabial flap for full thickness cheek defect involving large lip commisure. Both flaps having distinct advantage of relative ease in elevating flap and robust vascularity with acceptable aesthetic and functional outcome.
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Role of Imaging in Peritoneal Surface Malignancies
Abstract
Imaging plays a vital role in the evaluation of peritoneal malignancies. The presence of peritoneal metastases (PM) alters tumor staging, with direct implications in treatment choice and prognosis. Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) as a combined modality treatment have led to prolonged survival and even cure in selected patients with PM. Better outcomes are seen in patients with limited disease spread. Therefore, early diagnosis of peritoneal tumor seeding is essential. Despite significant advancement of technology, assessment of the origin of PM is often difficult, due partly to the complex peritoneal anatomy and partly due to the complex overlap of imaging features. Multidetector CT (MDCT) is the main stay due to its wide availbility, rapid evaluation, robust technique and good resolution. Imaging plays a vital role in selecting patients for the combined modality treatment. MRI is not as popular as CT due to limited availability, time required for the study and lack of experience with interpreting the results. PET-CT is useful in ruling out extra peritoneal disease and it is the CT component that is more reliable for predicting the disease extent. This article reviews the current use of various imaging modalities in various stages of treatment of patients with PM especially those undergoing CRS and HIPEC.
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Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer
Summary
Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m2/day on days 1–14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5–3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.
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Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India
Abstract
Background
The clinical phenotype of sickle cell disease (SCD) has been reported to be milder in India than in the United States. The objective of this large single-center study was to examine the rate of complications to define the phenotype of SCD in India.
Methods
The rate of complications per 100 person-years in 833 pediatric SCD patients for 1954 person-years in Nagpur, India including those diagnosed on newborn screen (NBS) and those presenting later in childhood (non-NBS) was compared to those reported in the cooperative study of sickle cell disease (CSSCD). Event rates were also compared between patients belonging to scheduled castes (SCs), scheduled tribes (STs), and other backward classes (OBC).
Results
Comparison of CSSCD versus Nagpur NBS versus Nagpur non-NBS for rates of pain (32.4 vs. 85.2 vs. 62.4), severe anemia (7.1 vs. 27 vs. 6.6), stroke (0.7 vs. 0.8 vs. 1.4), splenic sequestration (3.4 vs. 6.7 vs. 1.6), acute chest syndrome (24.5 vs. 23.6 vs. 1.0), and meningitis (0.8 vs. 0 vs. 0.1) revealed more frequent complications in Nagpur compared to CSSCD. Comparison of ST, SC, and OBC for rates of pain (84.6 vs. 71.9 vs. 63.5), acute chest syndrome (3.6 vs. 2.8 vs. 2.2), severe anemia (5.4 vs. 9.5 vs. 11.4), stroke (1.2 vs. 0.4 vs. 0.3), splenic sequestration (0.6 vs. 2.4 vs. 1.9), and meningitis (0.8 vs. 0 vs. 0.1) revealed significantly more frequent complications among ST.
Conclusions
SCD-related complications are more frequent in Indian children than that observed in CSSCD. Further study is indicated to define SCD phenotype in India.
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FDG-PET Identification of Infected Pulmonary Artery Conduit Following Tetralogy of Fallot (TOF) Repair
Abstract
Tetralogy of Fallot (TOF) is one of the most common forms of cyanotic congenital heart disease usually managed by serial surgical repairs. The repaired prosthetic valve or conduit is susceptible to life-threatening infection. FDG-PET is an effective alternative to evaluate the source of infection when other examinations are inconclusive. We report an unusual case of an infected pulmonary artery conduit after TOF repair although the echocardiogram was negative for vegetation, which was later confirmed by surgery and pathology. The case highlights the role of FDG-PET as a problem-solving tool for potential endocarditis and cardiac device infection cases after complex cardiac surgery.
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A two-year dyadic longitudinal study of mothers’ and fathers’ marital adjustment when caring for a child with cancer
Abstract
Objective
Studies examining interrelationships within parental couples confronted with pediatric cancer are scarce. This study explored dyadic longitudinal associations between both partners' family functioning and mood at diagnosis, and marital adjustment two years later.
Method
Parents of children (n = 47 couples) with acute lymphoblastic leukemia (ALL) completed the Family Well-Being Assessment and Profile of Mood States-Bipolar Form at diagnosis, and the Locke-Wallace Marital Adjustment Test two years post diagnosis. Multilevel linear models using the actor-partner interdependence model (APIM) and controlling for baseline marital adjustment were conducted to evaluate within subject and dyadic longitudinal effects.
Results
For mothers, better marital adjustment two years post diagnosis was associated with perception of greater family support and less role conflict and role overload at diagnosis. For fathers, better marital adjustment two years post-diagnosis was associated with perception of less role conflict, greater role ambiguity, and being more tired at diagnosis, as well as their partner's perception of less role conflict at diagnosis.
Conclusions
These findings highlight the importance of considering both partners' perspectives in understanding marital adjustment across treatment phases in parents of children with ALL. Early interventions for couples should be tailored to meet each partner's needs in order to foster resilience within the couple.
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Perception and Assessment of Verbal and Written Information on Sex and Relationships after Hematopoietic Stem Cell Transplantation
Abstract
This study aimed to investigate experiences of verbal and written information about sex and relationships among men and women treated with hematopoietic stem cell transplantation. The study also aimed to investigate the demand for information and assessment of the quality of written patient information material entitled "Sex and relationships in the treatment of blood diseases." Few studies exist that shed any light on the demand for information about sex and relationships on the part of patients with hematological diseases before, during, and after their treatment. A total of 216 patients undergoing treatment for malignant blood diseases between 2000 and 2010 participated in this study. Patients' experiences of information about sex and relationships, and their opinions about the written patient information, were assessed using a questionnaire created specifically for this study. Most patients (81 %) had not received information about sex and relationships from a healthcare professional. Almost 90 % of men felt that verbal information was important, compared with 82 % of women. The majority also held that written information was important. These results indicate that patients, regardless of gender, age, and treatment, consider oral and written information about sex and relationships to be important and that the healthcare system should provide the information. The written patient information was considered to play an important role in creating an opening for a conversation about a sensitive topic such as sexuality, and also as a source of reference and support for the patient and his/her partner.
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Tuberin Regulates Reactive Oxygen Species in Renal Proximal Cells, Kidney from Rodents and Kidney from TSC Patients
Abstract
Reactive oxygen species (ROS) are an important endogenous source of DNA damage and oxidative stress in all cell types. Deficiency in tuberin resulted in increase oxidative DNA damage in renal cells. In this study, role of tuberin in the regulating of ROS and NAD(PH)oxidases was investigated. ROS formation and NAD(P)H oxidases activity were significantly higher in mouse embryonic fibroblasts (MEF) and in primary culture of rat renal proximal tubular epithelial (RPTE) tuberin-deficient cells compared to wild type cells. In addition, Nox1, Nox2 and Nox4 (Nox isoforms) expression was higher in MEF and RPTE tuberin-deficient cells compared to wild type cells. Furthermore, NAD(P)H oxidases activity levels and protein expression of all Nox isoforms were higher in the renal cortex of rat deficient in tuberin. On the other hand, treatment of tuberin-deficient cells with rapamycin showed significant decrease in protein expression of all Noxs. Significant increase in PKCβII expression was detected in tuberin-deficient cells while inhibition of PKCβII by BMI resulted in decrease all Noxs protein expression. In addition, treatment of mice-deficient in tuberin with rapamycin resulted in significant decrease in all Noxs protein expression. Moreover, protein and mRNA expression of all Noxs were highly expressed in tumor kidney tissue of TSC patients compared to control kidney tissue of normal subjects. These data provide the first evidence that tuberin plays a novel role in regulating ROS generation, NAD(P)H oxidases activity and Noxs expression that may potentially involved in development of kidney tumor in TSC patients.
This article is protected by copyright. All rights reserved.
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Effect of adjuvant interferon therapy on hepatitis B virus-related hepatocellular carcinoma: a systematic review
Abstract
Objective
The objective of this study is to evaluate the efficacy of adjuvant interferon therapy for hepatitis B virus-related hepatocellular carcinoma (HCC) after different previous therapy.
Methods
An electronic search for articles about adjuvant treatment with IFN for patients with HCC published between 2000 and 2015 was conducted in MEDLINE, PubMed, Cochrane Library, and EMBASE databases. All data was tested with Stata12.0 software.
Results
Six trials with a total of 1054 subjects were screened according to inclusion and exclusion standards. Five hundred and seventeen HCC patients were treated with adjuvant treatment with IFN and 537 patients with placebo. Compared to the control group, both the recurrence rate and death rate of HCC in IFN group were statistically lower, especially after transhepatic arterial chemotherapy and embolization (TACE) treatment and both TACE and resection according to subgroup analysis.
There is no statistical significance on the both recurrence and death rate of HBV-related hepatocellular carcinoma after surgical resection treatment (RR = 0.96, 95 % CI, 0.84 to 1.1, p = 0.59 for recurrence and RR = 0.78, 95 % CI, 0.60 to 1.04, p = 0.09 for death rates).
Conclusions
Adjuvant IFN therapy may significantly reduced mortality as well as recurrence rate of patients with HBV-related HCC after no matter what the previous treatment. On the other hand, there is no statistical significance on the recurrence rate and mortality after surgical resection only. More research is needed into the relationship between effect of adjuvant interferon therapy and previous therapy, especially TACE.
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Targeting a Long Noncoding RNA in Breast Cancer
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Genomic Classification and Prognosis in Acute Myeloid Leukemia
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Roads Diverge — A Robert Frost View of Leukemia Development
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