Background and Objectives: The Anesthesiology Review Committee of the Accreditation Council for Graduate Medical Education sets core requirements for residency program accreditation. We periodically report and analyze the US anesthesiology residents' training experience in regional anesthesia and pain medicine. Methods: Resident caseload, procedure, and pain medicine evaluation data were aggregated for the resident cohort who graduated in 2015. These data were analyzed for present-day experience and compared with previous reports from years 1980, 1990, and 2000 graduates. Results: Data were available for 1631 residents who graduated from 129 training programs. Regional anesthesia as a portion of the overall anesthesiology residents' training experience remains unchanged since 1990. The distribution of regional anesthesia training has shifted from neuraxial to peripheral blocks. All residents at the 10th percentile and above achieved the benchmark for spinal, epidural, and peripheral nerve block anesthetics and for new pain evaluations. Conclusions: The focus of US anesthesiology resident training in regional anesthesia and pain medicine has changed over the past 15 years by shifting from neuraxial to peripheral nerve block techniques. Previous training deficits have resolved for spinal anesthesia and peripheral nerve block. Procedural experience in pain medicine overwhelmingly involves epidural and facet injections. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 13 Ιουνίου 2017
Biochemical and Pharmacological Characterization of a Mice Model of Complex Regional Pain Syndrome.
Background and Objectives: Complex regional pain syndrome is a challenging disease to treat. Recently, a mouse fracture model of complex regional pain syndrome has been developed that has many signs of the clinical syndrome. However, many aspects of the sensory neuron biochemistry and behavioral and pharmacological characterization of this model remain to be clarified. Methods: Mice were randomly assigned to fracture/cast or control (naive) groups. Fracture/cast mice underwent a closed distal tibia facture, with hindlimb wrapped in casting tape for 3 weeks. After cast removal, mice were tested for mechanical allodynia, burrowing behavior, and motor ability over a 12-week period. Protein immunohistochemistry was performed for substance P, calcitonin gene-related peptide, tropomyosin receptor kinase A, nerve growth factor, Nav1.7, and transient receptor potential cation-channel V1, colocalized in neurons, in the ipsilateral lumbar dorsal root ganglia (DRGs). Analgesic drugs were tested for pain-relieving efficacy. Results: Mechanical allodynia was greater in the ipsilateral hindpaw (P = 0.0002) in the fracture/cast group versus the control group, over the 3- to 12-week period. The amount of burrowing material removed was decreased (P = 0.0026), and there were deficits in spontaneous motor-rearing behavior (P = 0.018). Immunostaining of substance P, calcitonin gene-related peptide, Trk A receptor, nerve growth factor, Nav1.7, and transient receptor potential cation-channel V1 all demonstrated up-regulation in the DRGs of fracture mice versus controls (all P
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Stages of Change for Mammography Among Mexican Women and a Decisional Balance Comparison Across Countries
Abstract
An analysis of the adoption of secondary preventive behaviors is significant in regions with disparities in mammography use and breast cancer survival. Therefore, we determined the cognitive factors and the degree to which they differentiate stages of change in mammography among Mexican women. We also compared the decisional balance performance at Mexico, Switzerland, South Korea, and the USA. A cross-sectional study was designed for women in the stages of precontemplation (n = 240), contemplation (n = 243), action (n = 205), maintenance (n = 311), and relapse (n = 348). We only considered those ≥40 years with no cancer history. We measured the pros, cons, and self-efficacy, among other components. The decisional balance was estimated, and the result was transformed into T-scores. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with multinomial logistic regression using precontemplation as the reference group. The decisional balance distinguished stages partially: in contemplation, the OR was 1.26 (95%CI 1.08, 1.47) and in maintenance, 1.34 (95%CI 1.13, 1.59); in action and relapse, the statistical significance was marginal (p < 0.10). The decisional balance T-score performance registered variations among countries. Additionally, the effect of self-efficacy progressively ascended from contemplation to action and maintenance (OR = 1.29 [95%CI 1.05, 1.58], 1.53 [95%CI 1.20, 1.96], and 2.48 [95%CI 1.82, 3.39], respectively). Furthermore, risk perception and severity did not have an effect on stages of change among Mexican women. Recognition of what provokes action in a population is a key factor in the efficacy of screening programs. Variations among countries highlight the necessity for importance of investigating cognitive determinants for mammography in specific areas.
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Stages of Change for Mammography Among Mexican Women and a Decisional Balance Comparison Across Countries
Abstract
An analysis of the adoption of secondary preventive behaviors is significant in regions with disparities in mammography use and breast cancer survival. Therefore, we determined the cognitive factors and the degree to which they differentiate stages of change in mammography among Mexican women. We also compared the decisional balance performance at Mexico, Switzerland, South Korea, and the USA. A cross-sectional study was designed for women in the stages of precontemplation (n = 240), contemplation (n = 243), action (n = 205), maintenance (n = 311), and relapse (n = 348). We only considered those ≥40 years with no cancer history. We measured the pros, cons, and self-efficacy, among other components. The decisional balance was estimated, and the result was transformed into T-scores. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with multinomial logistic regression using precontemplation as the reference group. The decisional balance distinguished stages partially: in contemplation, the OR was 1.26 (95%CI 1.08, 1.47) and in maintenance, 1.34 (95%CI 1.13, 1.59); in action and relapse, the statistical significance was marginal (p < 0.10). The decisional balance T-score performance registered variations among countries. Additionally, the effect of self-efficacy progressively ascended from contemplation to action and maintenance (OR = 1.29 [95%CI 1.05, 1.58], 1.53 [95%CI 1.20, 1.96], and 2.48 [95%CI 1.82, 3.39], respectively). Furthermore, risk perception and severity did not have an effect on stages of change among Mexican women. Recognition of what provokes action in a population is a key factor in the efficacy of screening programs. Variations among countries highlight the necessity for importance of investigating cognitive determinants for mammography in specific areas.
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Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population
by Enjiao Zhang, Zhongfei Xu, Weiyi Duan, Shaohui Huang, Li Lu
BackgroundMicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.
MethodsThe genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the association. All analyses were performed using the SPSS software. 3.154() 0.001.
ResultsFor miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555–6.397, P value was 0.001). The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.
ConclusionsThese findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.
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Osteosarcoma of the lower limb metastasized to the septum and right side of the heart: a case report
Metastatic cardiac tumors are far more common than primary tumors. Although the hematogenous spread of osteosarcoma is well known, the imaging findings of cardiovascular involvement by osteosarcoma are seldom ...
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Coffee consumption and risk of non-Hodgkin’s lymphoma: evidence from the Italian multicentre case–control study
Abstract
Purpose
Several investigations have analysed the association between coffee intake and risk of cancer. Contradictory results were reported by the studies conducted in non-Hodgkin's lymphomas (NHL) few of which report results according to main NHL subgroups. The present study is aimed at evaluating the association between coffee consumption and the risk of NHL by analysing data from a large Italian multicentre case–control study that included 1,418 interviewed cases (1,301 B cell and 117 T cell NHL), diagnosed between 1990 and 1993, and 1,774 population healthy controls.
Methods
The association was evaluated by standard logistic regression analysis. Odds ratio (OR) estimates were adjusted for gender, age, residence area, educational level, previous chemotherapy treatment, smoking habit and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons.
Results
For all B cell lymphomas, an increased risk (OR 1.6, 95% CI 1.2–2.0) was observed in the highest exposure category (consumption >4 cups per day for at least 30 years), but without a clear dose–response trend. Subgroup analyses highlighted an increased risk for drinkers of at least four cups per day for follicular lymphoma (OR 2.0, 95% CI 1.2–3.4). The risk increased with years of exposure and was more elevated among current smokers.
Conclusions
Consumption of more than four cups of coffee per day enhances the risk of lymphoma, especially the follicular subtype. Further investigations based on large cohorts and accurate measures of exposure are needed to confirm the observed associations.
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Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity
Abstract
Purpose
The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity.
Methods
This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review.
Results
The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure.
Conclusions
We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.
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Propensity score-matching analysis of postoperative radiotherapy for stage IIIA-N2 non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database
Abstract
Background
To investigate the effects of postoperative radiotherapy (PORT) on the survival of patients with resected stage IIIA-N2 non-small cell lung cancer (NSCLC).
Methods
A total of 3,334 patients with resected stage IIIA-N2 NSCLC in 2004 to 2013 were identified in the Surveillance, Epidemiology, and End Results database and stratified according to use of PORT. Propensity score-matching (PSM) methods were used to balance the baseline characteristics of patients who did (n = 744) or did not (n = 744) undergo PORT. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared between these two patient groups.
Results
After PSM, PORT increased OS (hazard ratio, 0.793; p = 0.001) and LCSS (hazard ratio, 0.837; p = 0.022) compared with no PORT. The OS benefit for PORT was mainly seen in patients aged <60 years (5-year OS, 35.4% versus 28.9% for PORT versus no PORT, respectively; p = 0.026) and in those who underwent lobectomy (5-year OS, 43.5% versus 34.5% for PORT versus no PORT, respectively; p = 0.001). The LCSS benefit for PORT was significant in patients undergoing lobectomy (5-year LCSS, 48.3% versus 42.3% for PORT versus no PORT, respectively; p = 0.036).
Conclusions
The survival benefits of PORT were primarily observed in patients with resected stage IIIA-N2 NSCLC who were <60 years of age or had undergone lobectomy.
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Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity
Abstract
Purpose
The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity.
Methods
This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review.
Results
The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure.
Conclusions
We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.
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Propensity score-matching analysis of postoperative radiotherapy for stage IIIA-N2 non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database
To investigate the effects of postoperative radiotherapy (PORT) on the survival of patients with resected stage IIIA-N2 non-small cell lung cancer (NSCLC).
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The critical role of EBUS-TBNA cytology in the staging of mediastinal lymph nodes in lung cancer patients: A correlation study with positron emission tomography findings
BACKGROUND
The sensitivity and specificity of positron emission tomography (PET) have been significantly improved for the identification of malignancies in recent years; however, it is still necessary to confirm PET findings in a lymph node (LN) by direct tissue sampling. Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is the most commonly used approach for diagnosing and staging mediastinal LNs, particularly in lung cancer patients with locally advanced disease. Despite this fact, evidence-based studies of EBUS-TBNA cytology and PET findings are still suboptimal.
METHODS
The electronic database at the Johns Hopkins Medical Institutions and the pathology archives were searched to identify patients with mediastinal lymphadenopathy who had both EBUS-TBNA mediastinal LN sampling and a PET scan over a 14-month period. Patients suspected of having lung cancer and patients with a history of lung cancer were included in this study. Cytological diagnoses and follow-up surgical LN diagnoses were reviewed and correlated with PET scan findings.
RESULTS
A total of 140 LNs from 79 patients, including 86 PET-positive LNs and 54 PET-negative LNs, were included. The most frequently sampled LNs were 4R and 7. The average size of PET-positive and PET-negative LNs was 1.2 and 1.6 cm, respectively. Among PET-positive LNs, 41.9% were malignant, 41.9% showed reactive changes or granulomatous inflammation, and 9.3% were nondiagnostic by EBUS-TBNA. However, among PET-negative LNs, 74.1% showed reactive changes or granulomatous inflammation, 7.4% were malignant, and 18.5% were nondiagnostic by EBUS-TBNA.
CONCLUSIONS
The data demonstrate that EBUS-TBNA cytology improves the diagnostic accuracy of mediastinal LNs and clinical staging. Furthermore, EBUS-TBNA may identify additional malignant LNs (7.4%), and this highlights the risk for false-negative findings with PET scanning in isolation. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.
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Prognostic value of event-free survival at 12 and 24 months and long-term mortality for non-Hodgkin follicular lymphoma patients: A study report from the Spanish Lymphoma Oncology Group
BACKGROUND
Relatively few studies have analyzed the mortality of follicular lymphoma (FL) patients in comparison with a sex- and age-matched general population. This study analyzed the overall survival (OS) of patients with FL and compared their survival with the expected survival of a general population.
METHODS
Patients diagnosed with FL were prospectively enrolled from 1980 to 2013. Standardized mortality ratios (SMRs) were obtained from yearly sex- and age-specific mortality rates in Spain, and OS was compared with age- and sex-matched general population data.
RESULTS
A total of 1074 patients with newly diagnosed FL were enrolled. The median OS was 231 months (95% confidence interval [CI], 195-267 months). Event-free survival at 12 months (EFS12) and event-free survival at 24 months (EFS24) were associated with an increased probability of early death, with an SMR of 10.27 (95% CI, 8.26-12.77) for EFS12. The overall SMR, including all causes of death, was 2.55 (95% CI, 2.23-2.92), and it was higher for women (SMR, 3.02; 95% CI, 2.48-3.67) and young adults (SMR, 6.01; 95% CI, 3.13-11.55). More than 10 years after the diagnosis, mortality rates for FL patients were lower than those for the general population (SMR, 0.47; 95% CI, 0.28-0.78). When FL was excluded as a cause of death, the overall SMR was 1.35 (95% CI, 1.11-1.65) without a statistically significant mortality increase in the >60-year-old group in comparison with age- and sex-matched general population data. More than 15% of the patients included in the study (n = 158) had more than 10 years of follow-up.
CONCLUSIONS
EFS12 and EFS24 predict an early increase in mortality. The long-term SMR, over the course of 10 years of follow-up, shows that patients with FL have a risk of dying similar to that of a sex- and age-matched general population. Cancer 2017. © 2017 American Cancer Society.
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Association between patients' perception of the comorbidity burden and symptoms in outpatients with common solid tumors
BACKGROUND
Cancer patients' symptom burden is commonly attributed to their cancer and treatment. Increasingly, cancer patients have many other chronic comorbid conditions. However, the degree to which these comorbid conditions may contribute to the patient-reported symptom burden is unclear.
METHODS
This study explored the relations between the presence of comorbid conditions, the symptom experience and burden, and the perceived bother from cancer or comorbid conditions in 3106 cancer patients. The associations between the number of comorbidities (identified from current medications), the patient-reported symptom burden (the number of symptoms scored as ≥7 on the 13-item MD Anderson Symptom Inventory physical scale), the patient-reported bother from comorbid conditions and from cancer (from "not at all" to "extremely"), and the clinician-reported difficulty in caring for patients' symptoms were examined.
RESULTS
According to medication lists, 19% of the patients had at least 5 of 12 comorbid conditions. Approximately 39% rated at least 1 symptom as ≥ 7, and this proportion increased with an increasing number of comorbid conditions (48% with ≥ 5 comorbid conditions vs 36% with 1 comorbid condition). One-third of the patients reported moderate or worse bother, and this was significantly associated with an increased number of comorbid conditions (odds ratio [OR], 2.4) and an increased symptom burden (OR, 1.22). Clinician ratings of difficulty in managing patients' symptoms were significantly associated with bother from cancer (OR, 2.0), comorbid conditions (OR, 1.6), and symptom burden (OR, 1.1).
CONCLUSIONS
Comorbidity is common in cancer patients and is associated with a greater symptom burden and clinician reports of difficulty in managing patients' symptoms. Greater attention to comorbid conditions is needed to optimize the symptom management of cancer patients with multimorbidity. Cancer 2017. © 2017 American Cancer Society.
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Next-generation sequencing and clinical outcomes of patients with lung adenocarcinoma treated with stereotactic body radiotherapy
BACKGROUND
Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population.
METHODS
Under an Institutional Review Board-approved protocol, the records of 242 consecutive patients with early-stage lung cancers were reviewed; inclusion criteria included LAC histology with an adequate tumor sample for the successful use of next-generation sequencing and fluorescence in situ hybridization testing. Univariate analysis was performed to identify factors associated with clinical outcomes.
RESULTS
LAC samples from 98 of the 242 patients were reviewed (40.5%), of whom 45 patients (46.0%) had genetic testing. The following mutations were noted: KRAS in 20.0% of samples, BRAF in 2.2% of samples, SMAD family member 4 (SMAD4) in 4.4% of samples, epidermal growth factor receptor (EGFR) in 15.6% of samples, STK1 in 2.2% of samples, tumor protein 53 (TP53) in 15.6% of samples, and phosphatase and tensin homolog (PTEN) in 2.2% of samples. The following gene rearrangements were observed: anaplastic lymphoma kinase (ALK) in 8.9% of samples, RET in 2.2% of samples, and MET amplification in 17.8% of samples. The median total delivered SBRT dose was 50 grays (range, 48-60 grays) over a median of 5 fractions (range, 3-8 fractions). The KRAS mutation was associated with worse local control (odds ratio [OR], 3.64; P<.05). MET amplification was associated with worse regional (OR, 4.64; P<.05) and distant (OR, 3.73; P<.05) disease control.
CONCLUSIONS
To the authors' knowledge, the current series is the first to quantify genetic mutations and their association with clinical outcomes in patients with early-stage LAC treated with SBRT. KRAS mutations were associated with worse local control and MET amplification was associated with worse regional and distant disease control, findings that need to be validated in a prospective setting. Cancer 2017. © 2017 American Cancer Society.
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Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy
BACKGROUND
Osteoradionecrosis (ORN) of the mandible is a late toxicity affecting patients treated with radiotherapy for head and neck malignancies. To the authors' knowledge, ORN has no standardized grading system and its reporting is based on retrospective findings in heterogeneous patient populations. The rate of ORN in the era of intensity-modulated radiotherapy (IMRT) still is unknown.
METHODS
The authors report the incidence of ORN from prospectively collected data regarding 1196 patients who were diagnosed with squamous cell carcinoma of the oropharynx and treated with curative-intent IMRT, with or without concomitant systemic treatment, from January 2005 to December 2014. Each case of ORN was graded according to its severity. Clinical and dosimetric comparisons were performed between patients with ORN and a matched control cohort of patients without ORN.
RESULTS
The actuarial rate of ORN of the mandible was 3% at 1 year, 5% at 3 years, and 7% at 5 years. On multivariable analysis, smoking (hazard ratio, 1.9; 95% confidence interval, 1.07-3.4 [P = .03]) and T classification (hazard ratio, 1.78; 95% confidence interval, 1.02-3.1 [P = .041]) were found to be statistically significant risk factors. The presence of cardiovascular comorbidities, use of bisphosphonates, and pre-IMRT dental extractions were found to be different between the matched cohorts. The mandibular volume receiving 50 grays (Gy) (in cm3) and the volume receiving 60 Gy (in cm3) were found to be associated with ORN on multivariable analysis in the matched cohort patients receiving an IMRT regimen of 2 Gy per fraction.
CONCLUSIONS
ORN is relatively uncommon among patients with oropharyngeal carcinoma who are treated with IMRT, but continues to occur beyond 5 years after treatment. Modifiable risk factors that are associated with higher rates of ORN include smoking and the use of bisphosphonates. Minimizing the volumes of the mandible receiving >50 Gy or > 60 Gy also may have an effect on the ORN rate. Cancer 2017. © 2017 American Cancer Society.
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Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues
BACKGROUND
Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers.
METHODS
Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression.
RESULTS
Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1–positive versus PD-L1–negative tumors (P < .001).
CONCLUSIONS
A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017. © 2017 American Cancer Society.
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The association between germline BRCA2 variants and sensitivity to platinum-based chemotherapy among men with metastatic prostate cancer
BACKGROUND
Breast cancer 2 (BRCA2)-associated breast and ovarian cancers are sensitive to platinum-based chemotherapy. It is unknown whether BRCA2-associated prostate cancer responds favorably to such treatment.
METHODS
A retrospective analysis of a single-institution cohort of men with castration-resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate-specific antigen response to carboplatin-based chemotherapy. From 2001 through 2015, 8081 adult men with prostate cancer who had a consultation and/or underwent treatment at Dana-Farber Cancer Institute provided blood samples and consented to analyses of biologic material and clinical records. A subgroup of 141 men received at least 2 doses of carboplatin and docetaxel for castration-resistant disease (94% were also taxane refractory). These patients were categorized according to the absence or presence of pathogenic germline mutations in BRCA2 based on DNA sequencing from whole blood. The primary outcome was the response rate to carboplatin/docetaxel chemotherapy, defined according to a decline in prostate-specific antigen that exceeded 50% within 12 weeks of initiating this regimen. Associations between BRCA2 mutation status and response to carboplatin-based chemotherapy were tested using the Fisher exact test, with a 2-sided P value < .05 as the threshold for significance.
RESULTS
Pathogenic germline BRCA2 variants were observed in 8 of 141 men (5.7%; 95% confidence interval, 2.5%-10.9%). Six of 8 BRCA2 carriers (75%) experienced prostate-specific antigen declines >50% within 12 weeks, compared with 23 of 133 noncarriers (17%; absolute difference, 58%; 95% confidence interval, 27%-88%; P < .001). Prostate cancer cell lines functionally corroborated these clinical findings.
CONCLUSIONS
BRCA2-associated, castration-resistant prostate cancer is associated with a higher likelihood of response to carboplatin-based chemotherapy than non-BRCA2–associated prostate cancer. [See editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society.
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Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma
BACKGROUND
Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC).
METHODS
The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment.
RESULTS
In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3.
CONCLUSIONS
Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017. © 2017 American Cancer Society.
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A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma
Abstract
Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab. We performed an open-label single-arm phase II study of ipilimumab plus temozolomide in the frontline setting for patients with metastatic melanoma and LDH ≤2× upper limit of normal. Ipilimumab was given at 10 mg/kg on day 1 and temozolomide 200 mg/m2 orally days 1–4 every 3 weeks for four doses followed by maintenance ipilimumab every 12 weeks plus temozolomide every 4 weeks. The primary objective of the study was 6-month PFS. A total of 64 patients were enrolled and the 6-month PFS was 45% with median OS of 24.5 months. There were 10 (15.6%) confirmed partial responses and 10 (15.6%) confirmed complete responses. Duration of response amongst responders is 35 months with 10 patients demonstrating an ongoing response at median follow-up of 20 months. There were no deaths or unexpected toxicities on study. The most common gastrointestinal side effects were nausea and constipation rather than diarrhea or colitis. These results suggest that the combination of induction ipilimumab plus temozolomide could potentially be an effective strategy to enhance antitumor activity with a manageable toxicity profile. These findings warrant further evaluation in a large prospective study.
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A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma
Abstract
Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab. We performed an open-label single-arm phase II study of ipilimumab plus temozolomide in the frontline setting for patients with metastatic melanoma and LDH ≤2× upper limit of normal. Ipilimumab was given at 10 mg/kg on day 1 and temozolomide 200 mg/m2 orally days 1–4 every 3 weeks for four doses followed by maintenance ipilimumab every 12 weeks plus temozolomide every 4 weeks. The primary objective of the study was 6-month PFS. A total of 64 patients were enrolled and the 6-month PFS was 45% with median OS of 24.5 months. There were 10 (15.6%) confirmed partial responses and 10 (15.6%) confirmed complete responses. Duration of response amongst responders is 35 months with 10 patients demonstrating an ongoing response at median follow-up of 20 months. There were no deaths or unexpected toxicities on study. The most common gastrointestinal side effects were nausea and constipation rather than diarrhea or colitis. These results suggest that the combination of induction ipilimumab plus temozolomide could potentially be an effective strategy to enhance antitumor activity with a manageable toxicity profile. These findings warrant further evaluation in a large prospective study.
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Sulfhaemoglobinaemia caused by ferrous sulfate
A 78-year-old man was referred from his primary care clinic to the emergency department due to bluish discolouration of his lips and decreased oxygen saturation on pulse oximetry. The patient was asymptomatic. Physical exam was normal except for lip cyanosis. A CT pulmonary angiogram was negative for pulmonary embolism. Arterial blood gas (ABG) analysis with co-oximetry showed low oxyhaemoglobin, normal partial pressure of oxygen and methaemoglobinaemia, but an unexplained 'gap' in total haemoglobin saturation. This gap was felt to be due to sulfhaemoglobinaemia. After a thorough review of his medications, ferrous sulfate was stopped which resulted in resolution in patient's cyanosis and normalisation of his ABG after 7 weeks.
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Elevated risk of human papillomavirus-related second cancers in survivors of anal canal cancer
BACKGROUND
Over the last decade, the causal link between human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA) has been well described. Because HPV infection in one site is often associated with other sites of infection, it then follows that patients with SCCA may have an increased risk of additional HPV-related cancers. Identifying and targeting at-risk sites through cancer screening and surveillance may help to guide best practices. The current study sought to ascertain sites and risk of HPV-related second primary malignancies (SPMs) in survivors of SCCA.
METHODS
Using population-based data from 1992 through 2012, the authors identified patients with SCCA and determined their risk of HPV-related SPMs, including anal, oral, and genital cancers. Standardized incidence ratios (SIRs), defined as observed to expected cases, were calculated to determine excess risk.
RESULTS
Of 10,537 patients with SCCA, 416 developed HPV-related SPMs, which corresponded to an overall SIR of 21.5 (99% confidence interval [99% CI], 19.0-24.2). Men were found to have a higher SIR (35.8; 99% CI, 30.7-41.6) compared with women (12.8; 99% CI, 10.4-15.5). SIRs for a second SCCA were markedly higher in men (127.5; 99% CI, 108.1-149.2) compared with women (47.0; 99% CI, 34.7-62.1), whereas SIRs for oral cavity and pharyngeal cancers were elevated in men (3.1; 99% CI, 1.5-5.7) and women (4.4; 99% CI, 1.5-9.7). SIRs for sex-specific sites also were elevated, with male genital cancers having an SIR of 19.6 (99% CI, 8.7-37.6) and female genital cancers an SIR of 8.3 (99% CI, 6.1-11.0).
CONCLUSIONS
Patients with index SCCA are at an increased risk of subsequent HPV-related SPMs. The elevated risk is most striking in patients with second primary SCCAs; however, the risk of second cancers also appears to be increased in other HPV-related sites. Cancer 2017. © 2017 American Cancer Society.
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Exploiting DNA damage without repair: The activity of platinum chemotherapy in BRCA-Mutated prostate cancers
The report in this issue by Pomerantz and colleagues demonstrates that men with metastatic prostate cancer harboring germline BRCA2 mutations are strongly associated with a prostate-specific antigen response ≥50% during treatment with a platinum agent. However, more work will be required to classify other men who might benefit from platinum agents. See also pages 000-000.
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TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens
BACKGROUND
Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome.
METHODS
TP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon-based next-generation sequencing and Sanger sequencing.
RESULTS
TP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.2% (range, 5.6%-93.8%). The majority of mutations were single-nucleotide variants of missense type and involved the DNA-binding domain. TP53-mutated (TP53mut) ALL was found to be significantly associated with older age, lower median white blood cell and platelet counts, lower frequency of Philadelphia chromosome and a higher frequency of low hypodiploid karyotype compared with ALL with wild-type TP53 (TP53wt). To evaluate the prognostic effect of TP53 mutations, the authors selected 146 patients with B-cell immunophenotype ALL (24 with TP53mut and 122 with TP53wt) who were uniformly treated with frontline hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD)-based regimens; >90% of these individuals also received a monoclonal antibody. Over a median follow-up duration of 15 months, there was no significant difference in the median overall survival, event-free survival, and duration of complete remission noted between patients with TP53mut ALL and those with TP53wt ALL.
CONCLUSIONS
Hyper-CVAD-based regimens appear to negate the poor prognostic impact of TP53 mutations in patients with adult B-cell immunophenotype ALL. Cancer 2017. © 2017 American Cancer Society.
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microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients
Abstract
Purpose
α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up.
Methods
We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers.
Results
At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma.
Conclusions
The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.
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Intracellular vorinostat accumulation and its relationship to histone deacetylase activity in soft tissue sarcoma patients
Abstract
Purpose
In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects.
Methods
In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data. Cellular HDAC activity was evaluated using a fluorogenic assay. Concentration–response relationships were established between intracellular and extracellular vorinostat concentrations and HDAC inhibition in PBMCs.
Results
Pharmacokinetics of vorinostat and its two main inactive metabolites were determined over 8 h in plasma and PBMCs. Steady state AUCs (±SD) and T1/2 (±SD) were calculated to 4.61 ± 0.87 h µM and 1.73 ± 0.69 h (plasma) and 15.2 ± 9.03 h µM and 5.30 ± 4.27 h (PBMCs). Intracellular accumulation of vorinostat was determined together with prolonged vorinostat elimination in PBMCs. Cellular HDAC inhibition increased parallel with vorinostat concentrations in plasma and PBMCs. For effective inhibition of cellular HDACs (IC50) vorinostat concentrations of 0.05 µM in plasma and 0.17 µM in PBMCs were necessary.
Conclusion
HDAC inhibition closely followed intracellular vorinostat concentrations and was short-lasting, which may contribute to the limited efficacy seen with vorinostat in solid tumors so far.
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microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients
Abstract
Purpose
α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up.
Methods
We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers.
Results
At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma.
Conclusions
The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.
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Physician-to-physician communication in breast cancer care coordination.
| Related Articles |
Physician-to-physician communication in breast cancer care coordination.
Bull Cancer. 2017 Jun 08;:
Authors: Héquet D, Pouget N, Seror J, Huchon C, Robain M, Brédart A, Baffert S, Rouzier R
PMID: 28602384 [PubMed - as supplied by publisher]
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Middle ear adenoma with uncommon presentation and literature review
Middle ear adenoma (MEA) is a rare benign tumour. Here we report a case of MEA in a 39-year-old man with hearing loss. Some significant histopathological features of MEA and neuroendocrine differentiation identified by immunohistochemistry are described. The tumour showed remarkable and rare degenerative histological characteristics. There were a few tumour cells which were covered by degenerated tissue. Consequently, following frozen biopsy, the tumour was misdiagnosed as chronic ear inflammation. No recurrence was seen in this patient after 45 months of follow-up; regular clinical and radiological follow-up is necessary since recurrence is possible. A literature review for MEA is presented and this type of tumour is discussed clinically, microscopically and immunohistochemically. The differential diagnosis and associated treatment are described.
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Comparing Clinical Outcomes for Radium-223: Do Older Patients Do Worse?
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Yee Pei Song, Tracey Ellis, Richard Walshaw, Peter Mbanu, Omi Parikh, John Logue, Ananya Choudhury
PurposeTo examine the clinical benefits and toxicities of 223Ra in 2 different age groups of patients with castrate-resistant prostate cancer.Methods and MaterialsThis was a retrospective study of patients treated with 223Ra in 2 tertiary centers. Patients were divided into 2 different groups based on their age (≥72 years old and <72 years old). Treatment toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. Comparison of characteristics and outcome was carried out with the Mann-Whitney test and analysis of overall survival with the log-rank test.ResultsIn all, 129 patients were treated during the study period. Clinical benefit was similar in both groups. However, a statistically significant higher proportion of patients in the younger group had previously been treated with docetaxel. There was a higher rate of grade 3 anemia in younger patients.ConclusionsIn line with other studies, 223Ra was well tolerated with minimum toxicities. The significantly higher rate of grade 3 anemia in younger patients may be due to more cautious patient selection in the elderly population.
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Highly Accelerated Irradiation in 5 Fractions (HAI-5): Feasibility in Elderly Women With Early or Locally Advanced Breast Cancer
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Chris Monten, Yolande Lievens, Luiza Ana Maria Olteanu, Leen Paelinck, Bruno Speleers, Pieter Deseyne, Rudy Van Den Broecke, Wilfried De Neve, Liv Veldeman
PurposeTo investigate, in a prospective phase 1 to 2 trial, the safety and feasibility of delivering external beam radiation therapy in 5 fractions to the breast or thoracic wall, including boost and/or lymph nodes if needed, to women aged ≥65 years with breast cancer.Methods and MaterialsNinety-five patients aged ≥65 years, referred for adjuvant radiation therapy, were treated in 5 fractions over 12 days with a total dose of 28.5 Gy/5.7 Gy to the breast or thoracic wall and, if indicated, 27 Gy/5.4 Gy to the lymph node regions and 32.5 Gy/6.5 Gy to 34.5 Gy/6.9 Gy to the tumor bed. The primary endpoint was clinically relevant dermatitis (grade ≥2).ResultsMean follow-up time was 5.6 months, and mean age was 73.6 years. Clinically relevant dermatitis was observed in 11.6% of patients and only occurred in breast irradiation with boost (17.5% grade 2-3 vs 0% in the no-boost group). Although doses were high, treatment delivery with intensity modulated radiation therapy was swift, except for complex treatments, including lymph nodes for which single-arc volumetric modulated arc therapy was needed to reduce beam-on time.ConclusionAccelerated radiation therapy in 5 fractions was technically feasible and resulted in low acute toxicity. Clinically relevant erythema was only observed in patients receiving a boost, but still at an acceptable rate. Although the follow-up is still short, the results on acute toxicity after accelerated radiation therapy were encouraging. A 5-fraction schedule is well tolerated in the elderly and may lower the threshold for radiation therapy in this population.
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“But We Are Already Geriatric Oncologists”—Why Older Patients Need a Special Approach (A View from a United Kingdom Cancer Center)
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Anthea Cree, Tania Hawthorn, Laura Pemberton, Richard Cowan, Ananya Choudhury
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Radiation Therapy in Elderly Persons: An Old Issue With New Approaches
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Benjamin Movsas
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Improving Consistency and Quality of Care for Older Adults With Cancer: The Challenges of Developing Consensus Guidelines for Radiation Therapy
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Noam VanderWalde, Arti Hurria, Reshma Jagsi
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Frailty is our Destiny: An Introduction to the Red Journal's Special Edition on Radiation Therapy in the Elderly
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Anthony L. Zietman
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Communicating Effectively With Elderly Cancer Patients
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Mohamad H. Fakhreddine, Eva Galvan, Jamie Pawlowski, William E. Jones
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Breaking Up Is Hard to Do: Omission of Radiation Therapy for Select Women Aged >70 Years With Breast Cancer
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Jeffrey Peppercorn, Rachel Jimenez
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Influence of Age on Guideline-Concordant Cancer Care for Elderly Patients in the United States
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Penny Fang, Weiguo He, Daniel R. Gomez, Karen E. Hoffman, Benjamin D. Smith, Sharon H. Giordano, Reshma Jagsi, Grace L. Smith
PurposeTo examine the frequency of guideline-concordant cancer care in elderly patients, including "older" elderly (age ≥80 years).Methods and MaterialsUsing the Surveillance, Epidemiology and End Results–Medicare dataset in patients aged ≥66 years diagnosed with nonmetastatic breast cancer (n=55,094), non–small cell lung (NSCLC) (n=36,203), or prostate cancer (n=86,544) from 2006 to 2011, chemotherapy, surgery, and radiation (RT) treatments were identified using claims. Pearson χ2 tested associations between age and guideline concordance.ResultsOlder patients were less likely to receive guideline-concordant curative treatment: in stage III breast cancer, receipt of postmastectomy RT (70%, 46%, and 21% in patients aged 66-79, 80-89, and ≥90 years, respectively; P<.0001); in stage I NSCLC, RT or surgery (89%, 80%, and 64% in age 66-79, 80-89, and ≥90 years; P<.0001); in stage III NSCLC, RT or surgery plus chemotherapy (79%, 58%, and 27% in age 66-79, 80-89, and ≥90 years; P<.0001); and in intermediate/high-risk prostate cancer, RT or prostatectomy (projected life expectancy >10 years: 85% and 82% in age 66-69 and 70-75 years; and ≤10 years: 70%, 42%, and 9% in age 76-79, 80-89, and ≥90 years; P<.0001). However, older patients were more likely to receive guideline-concordant de-intensified treatment: in stage I to II node-negative breast cancer, hypofractionated postlumpectomy RT (9%, 16%, and 23% in age 66-79, 80-89, and ≥90 years; P<.0001); in stage I estrogen receptor–positive breast cancer, observation after lumpectomy (12%, 42%, and 84% in age 66-79, 80-89, and ≥90 years; P<.0001); in stage I NSCLC, stereotactic body RT instead of surgery (7%, 16%, and 25% in age 66-79, 80-89, and ≥90 years; P<.0001); and in lower-risk prostate cancer, no active treatment (25%, 54%, and 68% in age 66-79, 80-89, and ≥90 years; P<.0001).ConclusionActual treatment of older elderly cancer patients frequently diverged from guidelines, especially in curative treatment of advanced disease. Results suggest a need for better metrics than existing guidelines alone to evaluate quality and appropriateness of care in this population.
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Toward Personalized Cancer Care for Elderly Head and Neck Cancer Patients
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Ester Orlandi, Paolo Bossi
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Patterns of Care for Elderly Patients With Locally Advanced Head and Neck Cancer
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Jesus E. Juarez, Jehee Choi, Maie St John, Elliot Abemayor, Mindi TenNapel, Allen M. Chen
PurposeTo compare patterns of care for elderly patients aged ≥70 years with locally advanced head and neck cancer versus those of younger patients treated for the same disease.Methods and MaterialsThe medical records of 421 consecutive patients over the age of 50 years treated at a single institution between April 2011 and June 2016 for stage III/IV squamous cell carcinoma of the head and neck were reviewed. The primary treatment approach was compared using a t test statistic among 3 age cohorts: 50 to 59 years (118 patients); 60 to 69 years (152 patients); and 70 years and older (151 patients). Logistical regression was used to determine variables that influenced the likelihood of receiving surgery versus nonsurgical treatment, as well as radiation alone versus chemoradiation.ResultsThere was no difference in sex, T stage, N stage, Karnofsky performance status, or the number of chronic comorbid conditions among the 3 age cohorts (P>.05 for all). A greater proportion of elderly patients aged ≥70 years were treated by radiation alone compared with those aged 50 to 59 and 60 to 69 years (44% vs 16% and 24%, P=.01). Increasing age was associated with a greater likelihood of receiving primary nonsurgical versus surgical treatment (odds ratio 1.023, 95% confidence interval 1.004-1.042) and radiation alone compared with chemoradiation (odds ratio 1.054; 95% confidence interval 1.034-1.075). Ten chemotherapy regimens were used concurrently with radiation for patients aged ≥70 years, including carboplatin/paclitaxel (19%), carboplatin/cetuximab (19%), cisplatin (17%), and cetuximab (17%).ConclusionsDespite similar performance status and comorbidity burden compared with their younger counterparts, patients aged ≥70 years were more commonly treated with less-aggressive strategies, including radiation alone. The variability of concurrent chemotherapy regimens used further suggests that the standard of care remains to be defined for this population.
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Definitive Chemoradiation Therapy for Esophageal Cancer in the Elderly: Clinical Outcomes for Patients Exceeding 80 Years Old
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Cai Xu, Mian Xi, Amy Moreno, Yutaka Shiraishi, Brian P. Hobbs, Meilin Huang, Ritsuko Komaki, Steven H. Lin
PurposeThe optimal treatment approach for patients ≥80 years ("elderly") with esophageal cancer is not well established. We assessed the clinical outcomes in elderly patients treated with definitive chemoradiation therapy (CCRT) at our institution.Methods and Materials56 consecutive patients ≥80 years with esophageal cancer treated with conventional CCRT between 2001 and 2016 were propensity score matched 1:2 to generate 2 younger patient cohorts treated with CCRT without surgery: "intermediate" (65-79 years, n=112) and "younger" (<65 years, n=112). Treatment related toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The rates of overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method.ResultsThe median ages of the 3 cohorts were 81 years (elderly, 80-92 years), 71 years (intermediate, 65-79 years), and 58 years (younger, 20-64 years). The elderly cohort was more likely to have cardiac comorbidities. Although the clinical complete response (cCR) rate deviated significantly among the 3 cohorts, (78%, 72%, and 56%; P=.004), the data failed to identify statistically significant differences among RFS, 2-year, and 5-year OS, or in median survival, which was 15.5 months, 23.6 months, and 20.2 months (P=.468), respectively. The overall severe toxicity rates were 38%, 32%, and 30%, respectively (P=.644), including comparable rate of radiation pneumonitis (P>.05). The elderly cohort, however, did show statistically significant evidence of an increased rate of severe radiation pneumonitis (grade ≥3) which was observed to be 11% versus 4% and 0%, respectively (P=.003).ConclusionsThe studied elderly population showed evidence of similar long-term clinical efficacy after definitive CCRT when compared with cohorts of younger patients with similar prognostic status. An increased rate of pulmonary toxicity was identified, without evidence of differences for nonpulmonary severe adverse events. Understanding the prognostic risk factors of pulmonary toxicity after CCRT may effectuate improved long-term outcomes for elderly population.
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The Use of Hormone Therapy Alone Versus Hormone Therapy and Radiation Therapy for Breast Cancer in Elderly Women: A Population-Based Study
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Alan M. Nichol, Elisa K. Chan, Sarah Lucas, Sally L. Smith, Lovedeep Gondara, Caroline Speers, Scott Tyldesley
PurposeThe Cancer and Leukemia Group B (CALGB) 9343 trial randomized elderly women with estrogen receptor–positive, stage 1 breast cancer to receive either hormone therapy (HT) or HT and radiation therapy (HT-RT) after lumpectomy and showed no difference in survival. After this publication, a practice guideline made HT alone a standard treatment option in British Columbia. The subsequent population-based pattern of practice was studied.Methods and MaterialsAll women aged 70 to 79 years, referred after lumpectomy from 1999 to 2009, with stage 1, estrogen receptor–positive breast cancer were identified. The use of adjuvant HT or HT-RT was evaluated in 2 eras: before (1999-2003) and after (2005-2009) the CALGB publication. The proportion receiving each treatment in these eras was determined. Kaplan-Meier analyses with Cox regression were used for survival endpoints. The Fine and Gray method was used with non–breast cancer death as a competing risk for event-free survival. The Charlson score was used to quantify comorbidity. Adherence was defined as dispensation of 80% of prescribed HT.ResultsHT-RT was used in 91% of patients before (n=319) and 89% of patients after (n=403) the CALGB publication (P=.4). In the HT-alone group, the rate of HT adherence was 75% at 1 year and 55% at 4 years. The 10-year locoregional recurrence–free survival rate was 98% with HT-RT and 90% with HT alone (P=.01), whereas the 10-year breast cancer–specific survival rate was 96% with HT-RT and 95% with HT alone (P=.2). Patients with grade 3 histology or lymphovascular invasion were more likely to have low event-free survival. On multivariate analysis, treatment type did not predict overall survival (P=.3).ConclusionsOur patient outcomes closely matched those of the CALGB trial, suggesting that its results are generalizable to a population of elderly breast cancer patients with typical HT adherence. The CALGB trial results, as well as the resulting practice guideline, did not change the use of adjuvant HT-RT in our population-based cancer program.
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Timed Get Up and Go Test and Geriatric 8 Scores and the Association With (Chemo-)Radiation Therapy Noncompliance and Acute Toxicity in Elderly Cancer Patients
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Judith G. Middelburg, Mirjam E. Mast, Maaike de Kroon, Jan J. Jobsen, Tom Rozema, Huub Maas, Elizabet A. Baartman, Debby Geijsen, Annija H. van der Leest, Desirée J. van den Bongard, Judith van Loon, Tom Budiharto, Jan Willem Coebergh, Mieke J. Aarts, Henk Struikmans
PurposeTo investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent.Methods and MaterialsPatients were eligible if aged ≥65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT.ResultsWe investigated 402 patients with a median age of 72 years (range, 65-96 years). According to the G8, 44.4% of the patients were frail. Toxicity grade ≥3 was observed in 22% of patients who were frail according to the G8 and 9.1% of patients who were not frail. The difference was 13% (confidence interval 5.2%-20%; P=.0006). According to the TGUGT 18.8% of the patients were frail; 21% of the frail according to the TGUGT developed toxicity grade ≥3, compared with 13% who were not frail. The difference was 7.3% (confidence interval −2.7% to 17%; P=.11). Overall compliance was 95%. Toxicity was most strongly associated with type of primary tumor, chemotherapy, age, and World Health Organization performance status. Compliance was associated with type of primary tumor and age.ConclusionsThe usefulness of the TGUGT and G8 score in daily practice seems to be limited. Type of primary tumor, chemoradiotherapy, age, and World Health Organization performance status were more strongly associated with acute toxicity. Only chemoradiotherapy and age were associated with noncompliance. Overall the compliance was very high. To allow better-informed treatment decisions, a more accurate prediction of toxicity is desirable.
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The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Ronald Maggiore, Zachary S. Zumsteg, Karlynn BrintzenhofeSzoc, Kelly M. Trevino, Ajeet Gajra, Beatriz Korc-Grodzicki, Joel B. Epstein, Stewart M. Bond, Ira Parker, Julie A. Kish, Barbara A. Murphy, Noam A. VanderWalde
Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC—particularly those undergoing concurrent chemoradiation therapy—and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population.
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Use of Geriatric Assessment Tools in Selecting Therapies in Women Aged ≥70 Years With Hormone Receptor–Positive Early-Stage Breast Cancer: Preliminary Experience With a Quality Improvement Initiative
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Jean L. Wright, Arti Parekh, Yao Yao Pollock, Nancy Schoenborn, Karen L. Smith, Colette Magnant, Vered Stearns
PurposeTo develop a multidisciplinary algorithmic approach to management of women aged ≥70 years with clinically staged T1N0 hormone receptor–positive breast cancer, including geriatric assessments predicting life expectancy and the likelihood of functional decline in the near future, in the context of a program-wide quality improvement initiative, to better select patients for therapeutic interventions.Methods and MaterialsTwo geriatric assessment tools, the Combined Lee-Schonberg Index and the Vulnerable Elderly Scale, were introduced into our clinical workflow to predict long-term mortality and likelihood of functional decline. Scores from these tools, along with patient preferences and clinical features, were incorporated into a preoperative algorithm addressing the use of sentinel lymph node biopsy (SLNB), and a postoperative algorithm addressing the use of adjuvant radiation therapy (RT).ResultsThe algorithms were approved for use in August 2015. Twenty-four patients were identified by in-clinic screening and have been managed using the algorithms as a guide. Mean patient age was 80 years (range, 71-89 years). Per the preoperative algorithm, consideration of omission of SLNB was an option in 11 of 24 patients (46%), and in total 18 of 24 (75%) opted against SLNB. Per the postsurgical algorithm, consideration of omission of adjuvant RT was an option for 19 of 24 patients (79%), and in total 17 of 24 (71%) opted to forego RT.ConclusionIncorporation of simple geriatric assessments seems to have had a marked impact on decision making regarding both surgical and adjuvant therapies for women aged ≥70 years with early-stage hormone-positive breast cancer compared with historical patterns, with ≥71% omission of both SLNB and adjuvant RT in patients managed according to an institutional quality improvement initiative.
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Evaluation of Treatment Candidacy in Older Adults With Cancer
Publication date: 15 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 4
Author(s): Joe C. Huang, Upendra Parvathaneni
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Dual addressing of thymidine synthesis pathways for effective targeting of proliferating melanoma
Abstract
Here, we examined the potential of blocking the thymidine de novo synthesis pathways for sensitizing melanoma cells to the nucleoside salvage pathway targeting endogenous DNA irradiation. Expression of key nucleotide synthesis and proliferation enzymes thymidylate synthase (TS) and thymidine kinase 1 (TK1) was evaluated in differentiated (MITFhigh [microphthalmia-associated transcription factor] IGR1) and invasive (MITFmedium IGR37) melanoma cells. For inhibition of de novo pathways cells were incubated either with an irreversible TS inhibitor 5-fluoro-2′-deoxyuridine (FdUrd) or with a competitive dihydrofolate-reductase (DHFR) inhibitor methotrexate (MTX). Salvage pathway was addressed by irradiation-emitting thymidine analog [123/125I]-5-iodo-4′-thio-2′-deoxyuridine (123/125I-ITdU). The in vivo targeting efficiency was visualized by single-photon emission computed tomography. Pretreatment with FdUrd strongly increased the cellular uptake and the DNA incorporation of 125I-ITdU into the mitotically active IGR37 cells. This effect was less pronounced in the differentiated IGR1 cells. In vivo, inhibition of TS led to a high and preferential accumulation of 123I-ITdU in tumor tissue. This preclinical study presents profound rationale for development of therapeutic approach by highly efficient and selective radioactive targeting one of the crucial salvage pathways in melanomas.
FdUrd increases mitotic activity in melanoma cells and inhibits pyrimidine de novo synthesis pathway, leading to efficient uptake of salvage thymidine synthesis pathway targeting Auger electron-emitting thymidine analog 123/125I-ITdU. The DNA-incorporated 123/125I-ITdU induces severe DNA damages (double-strand breaks) and consequently cell apoptosis.
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Cervical spinal glioblastoma multiforme in the elderly
Spinal glioblastoma multiforme (GBM) is uncommon, and its diagnosis may be challenging. This is especially true in the elderly population. Best management strategy remains to be defined. The purpose of this report is to document this rare condition, increase awareness (as a potential differential diagnosis) and propose treatment options in the elderly; a review of the relevant literature is included. A biopsy may be beneficial in given circumstances as cervical spinal GBM carries a better prognosis compared with intramedullary metastasis.
http://ift.tt/2sWYxxY
Giant iridodialysis with wound dehiscence following penetrating keratoplasty: an ocular emergency
Description
Wound dehiscence is a known complication of keratoplasty which can occur even many years following the surgery. Usually trivial trauma is the causative factor for wound dehiscence, but spontaneous dehiscence has also been reported in the literature.1
A 45-year-old man presented with sudden loss of vision in the left eye following a blunt trauma. History revealed penetrating keratoplasty in the left eye for perforated corneal ulcer 2 years ago. On examination, visual acuity was hand movement close to face in the left eye and right eye being within normal limits with 20/20 visual acuity. Slit-lamp biomicroscopic examination showed broken monofilament nylon sutures leading to superior 6 clock hours (09:00 to 03:00 clock hours) of wound dehiscence, with corresponding 6 clock hours of giant iridodialysis prolapsing anteriorly (figure 1). The lens was completely extruded along with vitreous at the wound. Based on the relevant history and clinical findings, a...
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Toothpick-induced aortoenteric fistula presenting as sepsis
Aortoenteric fistulas (AEF) are a rare but life-threatening cause of gastrointestinal (GI) bleeding. We present the case of a primary AEF caused by ingestion of a toothpick by a 47-year-old male. This is the 10th known case in the literature in which a foreign body was found to be the cause of a communication between the aorta and the GI tract. Most foreign objects have been sewing needles; this is the first known case of a toothpick penetration. The patient presented to our institution with polymicrobial sepsis and bilateral pulmonary septic emboli. The patient was successfully treated but required multiple interventions and a prolonged intensive care unit admission.
http://ift.tt/2sX9qQy
A rare testicular vein anatomical variant contributes to right-sided varicocoele formation and leads to the diagnosis of renal cell carcinoma
Description
A man in his 60s presented for a testicular ultrasound due to asymptomatic scrotal swelling. Ultrasound showed a right-sided varicocoele (figure 1). A varicocoele is an abnormal dilatation of the pampiniform venous plexus in the scrotum. A renal ultrasound demonstrated a heterogeneous mass arising from the right kidney (figure 2). Histology subsequently revealed a renal cell carcinoma. CT identified duplication of the right testicular vein (figure 3). The first emptied into the inferior venacava (IVC) as expected. The second had a tortuous course arcing over the upper pole of the right kidney and emptying into the right renal vein (figure 4). Tumour extension into the right renal vein obstructed inflow from this accessory testicular vein and contributed to varicocoele formation (figure 5). Less than 1% of males have duplicate right testicular vein anatomy.1
http://ift.tt/2snBdN9
Bilateral persistent fetal vasculature: mimicker of retinoblastoma
We describe a case of bilateral persistent fetal vasculature (PFV) in a 3-month-old boy who presented with bilateral white pupillary reflex and a possible diagnosis of retinoblastoma. On ultrasonography, there was an echogenic band in the posterior segment of both eyes which connected the posterior surface of the lens capsule to the optic disc. Colour Doppler revealed the presence of vascularity in the band along its entire length. No calcification or mass lesion was seen. These findings are diagnostic of PFV. Most cases of PFV are unilateral and sporadic in nature and closely mimic retinoblastoma. Although rare, PFV should be considered in the differential diagnosis when examining a case of bilateral leukocoria. Paediatricians should be aware of this rare but serious entity.
http://ift.tt/2sX2J0V
A rare case of Mycobacterium abscessus subspecies abscessus prosthetic valve endocarditis and the clinical importance of inducible erm(41) gene testing
A 56-year-old man with a history of injection drug use and two prior episodes of native valve infective endocarditis presented with dyspnoea on exertion. Our preliminary work-up revealed bacteraemia with reported growth of 'Mycobacterium abscessus group' on multiple blood cultures. The patient was later found to have eustachian valve and prosthetic pulmonic valve endocarditis. Initially, he responded to standard antimycobacterial therapy for rapidly growing mycobacteria (RGM) with supporting laboratory susceptibilities. However, he later developed refractory disease and persistent bacteraemia in the setting of these alleged susceptible antibiotics. Further molecular testing revealed a functional and inducible erm(41) gene which confers macrolide resistance. A subspecies analysis of the M abscessus group revealed the subspecies to be abscessus. We present a challenging case of M abscessus subsp. abscessus bacteraemia and prosthetic valve endocarditis with further discussion on treatment and management of this infection along with the taxonomic complexity of this ubiquitous RGM.
http://ift.tt/2snAcEK
Unrecognised diaphragmatic hernia in a refugee child: an incidental diagnosis
A 4-year-old boy from Syria was evaluated at the emergency department because of an upper airway viral illness. His physical examination showed a significant intensity reduction of all heart sounds in the absence of any other pathological signs. As the child was affected with Down's syndrome and had suffered thoracic and abdominal trauma because of bombardments, a diaphragmatic hernia was immediately suspected and was confirmed through a simple chest X-ray. A careful clinical examination is crucial in refugee children and adolescents, as several medical and surgical disorders could have escaped previously.
http://ift.tt/2sWT0HT
Aberrant course of superficial radial nerve in the forearm: an anatomical variation and its clinical implications
The superficial radial nerve (SRN) is the terminal pure sensory branch of the radial nerve supplying dorsal aspects of the proximal portion of the lateral three and a half digits including the lateral two-thirds of the dorsum of the hand. It transits from its submuscular position to a subcutaneous position by passing between the brachioradialis and extensor carpi radialis longus tendons around 7 to 9 cm proximal to the radial styloid. We present a case where this nerve instead of its normal forearm course, pierced the brachioradialis tendon to become subcutaneous.
http://ift.tt/2snA2gJ
de Garengeot hernia with a mucinous neoplasm of the appendix, two clinical rarities combine to yield a first for the literature
Description
A woman in her 70s presented for a scheduled CT scan for workup of an adnexal lesion. The adnexa were within normal limits; however, a blind-ending tubular structure was noted in the right femoral canal (figures 1 and 2). The diagnosis of a de Garengeot hernia was made. This is a rare type of hernia that occurs when the appendix descends to lie in the femoral canal. Femoral hernias comprise roughly 3% of all abdominal wall hernias, and de Garengeot hernias comprises 0.8%–1% of all femoral hernias.1
Figure 1
CT scan axial images. Green arrows: dilated appendix in the right femoral canal with prominent adjacent soft tissue stranding.
Figure 2
CT scan sagittal slice. Green arrow: normal proximal appendix transitioning into abnormal, dilated distal appendix on entering the femoral canal.
...http://ift.tt/2sX8onM
Cardiac arrest following arteriovenous fistula manipulation: a cautionary note
Arteriovenous fistulas can lead to a number of different chronic complications. We describe a case where a patient developed a thrombosis within her brachiobasilic arteriovenous fistula, which was manually manipulated in order to restore fistula flow. This resulted in a pulseless electrical activity cardiac arrest within a few minutes. After ten minutes of chest compressions and intubation, there was return of spontaneous circulation. No epinephrine was given nor shocks administered. Patient was extubated within minutes and was alert, orientated and haemodynamically stable. CT pulmonary angiogram showed extensive bilateral pulmonary emboli. Manual manipulation of the arteriovenous fistula lead to significant amounts of thrombus embolising to the pulmonary arteries, and resultant cardiac arrest due to circulatory compromise. Chest compressions likely dislodged these emboli, allowing circulation to recommence. We publish this as a cautionary note of a rare but potentially fatal complication.
http://ift.tt/2snqdPB
Retroperitoneal haemangiopericytoma
A 55-year-old woman, diagnosed with a renal mass by abdominal ultrasonography (USG) in an external medical centre, presented to our hospital. The medical history was unremarkable except for diabetes mellitus and hypertension. The haemogram and urine tests were normal. The only pathology revealed in routine biochemistry tests was increased glucose level (164âmg/dL). The repeat USG performed in our hospital revealed a solid hypoechoic mass lesion approximately 4âcm in diameter closely adjacent to the right kidney. At Doppler ultrasonography, the tumour demonstrated intense vascularisation. An abdominal CT scan was performed to characterise the lesion. The CT scan revealed a 42×39âmm mass lesion with regular contours adjacent to the right kidney. In the arterial phase, the tumour demonstrated intense enhancement and in the delayed phase the images showed washout (figure 1). The patient underwent surgery and after histopathological examination retroperitoneal haemangiopericytoma was diagnosed and no relapse or distant organ metastasis was detected throughout the 2-year follow-up.
http://ift.tt/2sX13V9
Shoulder pain in smokers could be a life changer
Case history
A 51-year-old Saudi man presented to us with a 4-week history of right shoulder and chest pain radiating to the back. He also had distal and proximal muscle weakness of the right upper limb.
He is a chronic smoker for 40 years, about three packs per day. His lifetime exposure to tobacco was 120 pack years. He lost about 3 kg in the last 1 week. There was no history of cough or shortness of breath or fever with night sweats.
He had a history of pulmonary tuberculosis 28 years ago and taken complete treatment for 1 year.
On examination, there was ptosis, enophthalmos, narrowing of palpebral fissure and miosis of the right eye and anhidrosis of the right half of the face (figure 1). He also had clubbing of fingers.
Figure 1
Ptosis and miosis in the right eye.
The motor system examination...
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Isolation and characterization of trophoblasts from enzymatic explants of human term placenta
Abstract
In the present study, we describe a new method of isolation and culture of human villous and extravillous trophoblasts from term placenta. The cultivation of trypsinized placental villous tissue explants, followed by the isolation of cells from outgrowth islets allows for obtaining a cytotrophoblast subpopulation that is free from contamination by other cell types. Compared to other methods, our protocol is mild, simple and effective, does not request costly reagents and provides isolation of the mononuclear cytotrophoblast cell populations free from contamination by other types of placental cells. The isolated cells proliferated and formed a pleomorphic monolayer, where cells fused into a small number of binuclear or polynuclear syncytiotrophoblasts. Isolated cytotrophoblast cells expressed the specific epithelial intermediate filament cytokeratin 7 (CK7), the epithelium-specific cell–cell adhesion molecule E-cadherin and were CD9-, CD45- and vimentin-negative. Cyto- and syncytiotrophoblasts obtained by this method can be used as a model or tool for the fundamental research of differentiation and function of human placental cells, and can provide a new understanding of drug distribution in placenta. Their combination with other in vitro cell models can be useful for studying a variety of other aspects concerning placental functions, which will provide new knowledge for understanding immunology, endocrinology and development of placenta.
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Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma
Marwa Mohammed Serag Eldien, Asmaa Gaber Abdou, Tarek Rageh, Eman Abdelrazek and Enas Elkholy
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Primary Occipital Ewing’s Sarcoma with Subsequent Spinal Seeding
Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.
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Cytomegalovirus duodenitis in immunocompetent patients: what else should we look for?
Cytomegalovirus (CMV) infection is a well-recognised complication of immunodeficiency, although the burden of CMV disease in immunocompetent adults is still unknown. We present the case of a 54-year-old male patient admitted due to severe diarrhoea, epigastric pain and fever. Initial diagnostic workup revealed pericardial and pleural effusion, enlarged abdominal lymph nodes and mild elevation of liver enzymes. CMV serology was IgM positive, and upper endoscopy revealed proximal enteritis. Histology and immunohistochemistry of duodenal samples confirmed CMV disease. An extensive investigation of possible immunodeficiency was conducted with positron emission tomography (PET) scan revealing an abnormal hypermetabolic pulmonary nodule. The patient underwent a right superior lobectomy which, on analysis, confirmed an atypical bronchopulmonary carcinoid tumour. We report this case to reinforce the importance of considering CMV infection as a differential diagnosis in apparent immunocompetent patients and to emphasise the importance of looking for any condition that may cause any degree of immune dysfunction.
http://ift.tt/2rlGtRj
Go-karting injury: a case of laryngeal trauma
We report a case of accidental strangulation and crush injury to the anterior neck resulting in laryngeal trauma. This extremely uncommon mechanism of injury provides a safety warning regarding precautions with neck wear, and the unusual resulting injury represents an opportunity to review best practice in management of laryngeal trauma.
http://ift.tt/2s5sWKw
Follicular dendritic sarcoma masquerading as fibrosing mediastinitis
Fibrosing mediastinitis (FM) is a rare disorder resulting from abnormal immunological-mediated fibro-proliferative reaction in the mediastinum. Here, we describe a case of a 46-year-old female with an incidentally found 11x9 cm posterior mediastinal mass. Multiple biopsies of this unresectable, 18-fluorodeoxyglucose avid mass revealed marked fibrosis without any evidence of malignancy, suggesting idiopathic fibrosing mediastinitis as our initial diagnosis. Multiple interventions including a trial of steroids, fluconazole, and azathioprine to target fibrosing mediastinitis were not successful. Repeat biopsy was consistent with primary mediastinal follicular dendritic cell sarcoma. The manuscript highlights the heightened need for suspecting occult malignancies in cases of FM presenting with an indeterminate cause.
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Rapid development and recurrence of translocation renal cell carcinoma
Translocation renal cell carcinoma (RCC) is a rare aggressive malignancy in adults. A 40-year-old man presented with painless macroscopic haematuria. Initial investigations of renal ultrasound, CT scan, urine culture and urine cytology were normal. On rigid cystoscopy and pyelo-ureteroscopy, bleeding was seen from a normal-appearing right renal upper pole. An arteriovenous malformation was suspected, and laser cautery was performed. Left renal biopsy was performed due to proteinuria and suggested IgA nephropathy. The patient represented with haematuria and repeat imaging only 17 months after first presentation displayed a 9.8 cm right renal tumour with renal vein thrombus. An upper tract urothelial cancer was suspected, and the patient underwent right nephroureterectomy. Histopathology revealed translocation RCC, completely excised. Ten months postoperatively, metastasis was seen on surveillance imaging and subsequently confirmed on biopsy. The patient was referred for systemic therapy and remains alive 19 months postprocedure.
http://ift.tt/2s5pUG4
A large chronic pericardial effusion in an ultramarathon runner with anti-CCP positive rheumatoid arthritis
Pericardial effusions arise as an extra-articular manifestation of rheumatoid arthritis (RA). Pericardial effusions are often asymptomatic, particularly in the early phase, but patients are at risk of cardiac tamponade as the effusion progresses. We discuss the case of a 40-year-old male ultramarathon runner with RA who presented with mild pleuritic chest pain and exertional dyspnoea after a recent long-haul flight. Despite a relative tachycardia, his observations were otherwise unremarkable. His blood tests revealed a C-reactive protein (CRP) of 86 mg/L and an anti-cyclic citrullinated peptide (anti-CCP) titre of 360 units/mL. He was initially diagnosed with a pulmonary embolism; however, a large pericardial effusion was found incidentally on CT pulmonary angiogram with over 1500 mL subsequently drained. The patient's symptoms resolved and CRP normalised 2 weeks later. This unique case illustrates that physically fit patients may physiologically compensate for large pericardial effusions and that arthritic symptoms do not correlate with the severity of extra-articular features in RA.
http://ift.tt/2rkSoPn
Incidental bilateral optic nerve hypoplasia
Description
A 19-year-old man was incidentally noted to have a bitemporal heteronymous hemianopia on automated perimetry during his first optician's sight test (figure 1). The patient reported life-long reduced vision in the right eye although this was his first presentation to ophthalmic services. The patient was induced at 34 weeks due to poorly controlled gestational diabetes in his mother. The patient had no other ocular, medical, drug or family history.
Figure 1
24-2 Humphrey Visual Field Test demonstrating a bitemporal heteronymous hemianopia.
On examination, visual acuity was 6/9 in the right eye and 6/6 in the left eye. The anterior segment was normal. Funduscopy demonstrated bilateral hypoplastic optic discs with the characteristic 'double-ring sign' (figure 2). The disc diameter to disc–macula distance ratios were 0.33 and 0.31 in the right and left eyes, respectively (figure 3)....
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Angle closure as a cause for intermittent headache in a child
Angle closure is usually associated with older patients, as it typically manifests in middle to later life, being associated with an age-related increased lens volume. However, angle closure can occur in any age group if there is an anatomical predisposition that promotes pupillary block or an anterior pulling of the iris. During an acute angle closure, patients generally experience ocular pain, headache, nausea, vomiting and conjunctival hyperaemia. These attacks can be misinterpreted as migraine, particularly if subacute or chronic and the demographic characteristics of the patient do not suggest a primary angle closure event. Diagnosing a headache as ocular related is of paramount importance, since there is an effective treatment. We report a case of a child with intermittent headache which revealed a subacute angle closure in both eyes.
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Fetal MRI of thoraco-omphalopagus conjoined twins
Description
Conjoined twins are very rare with incidence of 1 per 250 000 live births.1 Fetal MRI is an important adjunct to ultrasound particularly in evaluation of complex fetal anomalies and organ positions.2 3 This case report illustrates our first experience in MRI fetal of conjoined twins with the current available sequences.
An 18-year-old G2 P0+1, with no known medical illness, was diagnosed with conjoined twin pregnancy from antenatal ultrasound at 28 weeks. MRI of pelvis was performed using a 1.5 T Phillips using torso array coil. Sequences employed were Coronal T2 FB (free breathing), Axial T2 FB, Sagittal T2 FB, BB_SSh_Rtrig SE, Axial BTFE and BB_SSh_RTrig SE. The effective time echoof 188 s, 10 mm slice thickness. Each slice was performed in 2s, and the full sequences in each imaging plane require 27 s, 256x256 matrix and 34 cm field of view.
It showed conjoined twins with single and fused heart,...
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