Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 6 Απριλίου 2017
OnabotulinumtoxinA injections in detrusor facilitate self-catheterisation in a patient with paraplegia and bladder outlet dyssynergia
This case report describes the case of improvement of clean intermittent catheterisation procedures after each intradetrusor administration of onabotulinumtoxinA in a 45-year-old man with L1 paraplegia with neurogenic detrusor overactivity and bladder outlet dyssynergia.On three occasions, improvement on clean intermittent catheterisation procedures appeared 10 to 14 days after intradetrusor injections of onabotulinumtoxinA and lasted for 9 months. We hypothesise a possible influence of intravesical injections of onabotulinumtoxinA on the storage reflex. We also discuss the possibility of a dispersion of onabotulinumtoxinA towards contiguous structures such as the urethral sphincter.
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Postmastectomy radiation therapy for breast cancer patients with one to three positive lymph nodes: a propensity score matching analysis
Future Oncology Ahead of Print.
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High blood tacrolimus and hyperkalemia in a heart transplant patient
Annals of Cardiac Anaesthesia 2017 20(2):270-271
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Anger: An enemy of heart, raj yoga meditation is heart friendly
Annals of Cardiac Anaesthesia 2017 20(2):127-128
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Inverted left atrial appendage masquerading as a left atrial mass
Annals of Cardiac Anaesthesia 2017 20(2):248-249
An inverted left atrial appendage after cardiac surgery is a rare finding and can be misinterpreted as a thrombus, mass, or vegetation. We report a case where intraoperative transesophageal echocardiography assisted in making an accurate diagnosis.
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Artificial intelligence in mitral valve analysis
Annals of Cardiac Anaesthesia 2017 20(2):129-134
Background: Echocardiographic analysis of mitral valve (MV) has become essential for diagnosis and management of patients with MV disease. Currently, the various software used for MV analysis require manual input and are prone to interobserver variability in the measurements. Aim: The aim of this study is to determine the interobserver variability in an automated software that uses artificial intelligence for MV analysis. Settings and Design: Retrospective analysis of intraoperative three-dimensional transesophageal echocardiography data acquired from four patients with normal MV undergoing coronary artery bypass graft surgery in a tertiary hospital. Materials and Methods: Echocardiographic data were analyzed using the eSie Valve Software (Siemens Healthcare, Mountain View, CA, USA). Three examiners analyzed three end-systolic (ES) frames from each of the four patients. A total of 36 ES frames were analyzed and included in the study. Statistical Analysis: A multiple mixed-effects ANOVA model was constructed to determine if the examiner, the patient, and the loop had a significant effect on the average value of each parameter. A Bonferroni correction was used to correct for multiple comparisons, and P = 0.0083 was considered to be significant. Results: Examiners did not have an effect on any of the six parameters tested. Patient and loop had an effect on the average parameter value for each of the six parameters as expected (P < 0.0083 for both). Conclusion: We were able to conclude that using automated analysis, it is possible to obtain results with good reproducibility, which only requires minimal user intervention.
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Erratum: Percutaneous tracheostomy in patients on anticoagulants
Annals of Cardiac Anaesthesia 2017 20(2):282-282
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Forbidden word entropy of cerebral oximetric values predicts postoperative neurocognitive decline in patients undergoing aortic arch surgery under deep hypothermic circulatory arrest
Annals of Cardiac Anaesthesia 2017 20(2):135-140
Purpose: Up to 53% of cardiac surgery patients experience postoperative neurocognitive decline. Cerebral oximetry is designed to detect changes in cerebral tissue saturation and therefore may be useful to predict which patients are at risk of developing neurocognitive decline. Methods: This is a retrospective analysis of a prospective study originally designed to determine if treatment of cerebral oximetry desaturation is associated with improvement in postoperative cognitive dysfunction in patients undergoing aortic reconstruction under deep hypothermic circulatory arrest. Cognitive function was measured, preoperatively and 3 months postoperatively, with 15 neuropsychologic tests administered by a psychologist; the individual test scores were summed and normalized. Bilateral cerebral oximetry data were stored and analyzed using measures of entropy. Cognitive decline was defined as any decrease in the summed normalized score from baseline to 3 months. Results: Seven of 17 (41%) patients suffered cognitive decline. There was no association between baseline cerebral oximetry and postoperative cognitive dysfunction. Nor were changes in oximetry values associated with cognitive decline. However, cognitive decline was associated with loss of forbidden word entropy (FwEn) (correlation: Rho ρ = 0.51, P = 0.037 for left cerebral oximetry FwEn and ρ = 0.54, P = 0.025 for right cerebral oximetry FwEn). Conclusion: Postoperative cognitive decline was associated with loss of complexity of the time series as shown by a decrease in FwEn from beginning to end of the case. This suggests that regulation of cerebral oximetry is different between those who do and those who do not develop cognitive decline.
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Partial anomalous pulmonary venous return: Scimitar vein
Annals of Cardiac Anaesthesia 2017 20(2):259-261
Scimitar syndrome is a rare association of congenital cardiopulmonary anomalies characterized by partial anomalous pulmonary venous return, in which an abnormal right pulmonary vein drains into the inferior vena cava. This case exemplifies the role of transesophageal echocardiography in perioperative management and surgical decision-making.
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An analysis of the factors producing multiple ventricular arrhythmias during pulmonary artery catheterization
Annals of Cardiac Anaesthesia 2017 20(2):141-144
Background: The development of arrhythmias during placement of a pulmonary artery catheter (PAC) is common. Aims: This study was designed to examine factors influencing development of ventricular arrhythmias in adult patients undergoing cardiovascular operations during the catheter placement. Settings and Designs: Prospective, observational, cohort study. Methods: We prospectively studied 174 patients undergoing cardiovascular operations. A PAC was inserted through the right internal jugular vein by staff anesthesiologists. Electrocardiography tracings were recorded as the catheter was advanced from the right atrium to the pulmonary artery. Arrhythmias were classified as absent, single, or multiple (two or more consecutive) ventricular arrhythmias. We examined risk factors to produce ventricular arrhythmias during the placement. Statistical Analysis: The data were analyzed using logistic regression analysis to assess factors for the occurrence of ventricular arrhythmias after univariate analyses. Results: Ventricular arrhythmias (single and multiple) occurred in 149 patients (85.6%) and multiple arrhythmias were observed in 78 patients (44.8%). There were no factors to facilitate the ventricular arrhythmias (single and multiple), whereas it showed that valvular diseases (P = 0.049) and the placement time (P < 0.001) are significant factors to produce multiple arrhythmias. Conclusion: Both valvular diseases and long placement time were significant risk factors to produce multiple ventricular arrhythmias during placement of a PAC.
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Importance of 3D real time perioperative tee in ASD device embolisation
Annals of Cardiac Anaesthesia 2017 20(2):278-278
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Carotid artery disease and periprocedural stroke risk after transcatheter aortic valve implantation
Annals of Cardiac Anaesthesia 2017 20(2):145-151
Objective/Background: To examine the role of carotid stenosis (CS) and other independent risk factors of perioperative stroke, following transcatheter aortic valve implantation (TAVI). Materials and Methods: Using data from the National Inpatient Sample database for analysis, patients who underwent TAVI were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Various preoperative and perioperative risk factors and their association with perioperative strokes were studied. Results: Data on 7566 patients who underwent a TAVI procedure from 2012 to 2013 were extracted. The average age of the patient population was 81.2 ± 0.32 years. The overall perioperative stroke rate in our patient cohort was 2.79%. Majority (94.6%) of the strokes were ischemic. Multivariate analysis showed the following independent risk factors for perioperative strokes after TAVI: female gender odds ratio (OR) = 2.25 (95% confidence interval [CI], 1.42–3.57), higher van Walraven score OR = 6.6 (95% CI = 3.71–11.73), bilateral CS OR = 4.46 (95% CI = 2.03–9.82), and TAVI with a cardiac procedure done under cardiopulmonary bypass OR = 2.84 (95% CI = 1.57–5.14). Conclusion: Bilateral carotid disease is a significant risk factor for perioperative strokes following TAVI. Preoperative screening with carotid Doppler to identify high-risk patients appears to be warranted. In addition, patients of female gender were found to have an increased risk for carotid disease.
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Transthoracic echocardiography versus transesophageal echocardiography for rupture sinus of Valsalva aneurysm
Annals of Cardiac Anaesthesia 2017 20(2):245-246
We report a rare case of sinus of Valsalva aneurysm of both right and left coronary sinus (LCS), with perforation of the LCS opening into the left ventricle. The LCS aneurysm with its perforation was undiagnosed on transthoracic echocardiography emphasizing the role of transesophageal echocardiography in delineating the anatomy.
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Impact of dexmedetomidine on hemodynamic changes during and after coronary artery bypass grafting
Annals of Cardiac Anaesthesia 2017 20(2):152-157
Objective: To determine the effect of dexmedetomidine (Dex) on hemodynamic changes during cardiopulmonary pump and postoperative period in coronary artery bypass grafting (CABG). Methods and Design: This study is designed as a double-blinded, randomized clinical trial. Setting: University hospital and single center. Participants: patients candidate for elective CABG. Intervention: Dex 0.5 μg/kg/h or placebo was infused from the initiation of anesthesia up to extubation in Intensive Care Unit (ICU). Measurements: Heart rate (HR) and blood pressure (BP), pain score, and total morphine dose requirement were monitored and compared during cardiac pump up to 12 h postoperative in ICU. Results: Mean arterial pressure was significantly higher in Dex group in postoperation period at 1 (P = 0.010) and 2 h (P = 0.002) compared to control group. HR was significantly lower in Dex group in postcardiopulmonary bypass (CPB) time at 0 h (P = 0.001), 1 h (P = 0.0016), and 2 h (P = 0.001), and then in postoperative period in ICU at 1 h (P = 0.025), 2 h (P = 0.0012), and 4 h (P = 0.0025) compared to control group. Postoperative pain score was significantly lower during 12 h after surgery. Conclusion: Dex could effectively blunt hemodynamic response to surgical stress, particularly during CPB pump and afterward. Infusion of Dex maintains BP at higher range and HR at lower range compared to placebo.
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Mechanical cause for acute left lung atelectasis after neonatal aortic arch repair with arterial switch operation: Conservative management
Annals of Cardiac Anaesthesia 2017 20(2):252-255
Respiratory complications due to mechanical obstruction of the airways can occur following pediatric cardiac surgery. Clinically significant intrathoracic vascular compression of the airway can occur when extensive dissection and mobilization of arch and neck vessels is involved as in repair of interrupted aortic arch. This case report describes a neonate who underwent interrupted aortic arch repair along with an arterial switch operation and developed a left lung collapse immediately after tracheal extubation. Fiber-optic bronchoscopy revealed vascular compression as the real culprit. The child was successfully managed conservatively.
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The role of Rajyoga meditation for modulation of anxiety and serum cortisol in patients undergoing coronary artery bypass surgery: A prospective randomized control study
Annals of Cardiac Anaesthesia 2017 20(2):158-162
Introduction: Rajyoga meditation is a form of mind body intervention that is promoted by the Brahma Kumaris World Spiritual University. This form of meditation can be easily performed without rituals or mantras and can be practiced anywhere at any time. The practice of Rajyoga meditation can have beneficial effects on modulating anxiety and cortisol level in patients undergoing major cardiac surgery. Materials and Methods: A prospective randomized control study was carried out in a single tertiary care center. One hundred and fifty patients undergoing elective coronary artery bypass surgery were enrolled in the study. The patients were randomized in two groups namely, Group 1 (Rajyoga group) and Group 2 (Control Group). Anxiety was measured on a visual analog scale 1–10 before the start of Rajyoga training or patient counseling (T1), on the morning of the day of surgery (T2), on the 2nd postoperative day (T3), and on the 5th postoperative day (T4). The serum cortisol level was measured in the morning of the day of surgery (T1), on the 2nd postoperative day (T2) and on the 5th postoperative day (T3), respectively. Results: In the study, it was seen that the anxiety level of the patients before the surgery (T1) and on the day of surgery (T2) were comparable between the two groups. However on the 2nd postoperative day (T3), the patients who underwent Rajyoga training had lower anxiety level in comparison to the control group (3.12 ± 1.45 vs. 6.12 ± 0.14, P < 0.05) and on the 5th postoperative day (T4) it was seen that Rajyoga practice had resulted in significant decline in anxiety level (0.69 ± 1.1 vs. 5.6 ± 1.38, P < 0.05). The serum cortisol level was also favorably modulated by the practice of Rajyoga meditation. Conclusion: Mindbody intervention is found to effective in reducing the anxiety of the patients and modulating the cortisol level in patients undergoing wellknown stressful surgery like coronary artery bypass surgery.
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Modified blalock-taussig shunt and levosimendan for left ventricular preparation in a child with transposition of great arteries and regressed ventricle undergoing rapid 2 stage arterial switch operation
Annals of Cardiac Anaesthesia 2017 20(2):265-267
Rapid two-stage arterial switch operation (ASO) is very relevant as many patients of transposition of great arteries (TGA) present late to the hospital when primary switch either is not possible or carries a high risk of morbidity and mortality. Hence, other means apart from the traditional methods of left ventricle preparedness should be tried to help this category of patients, who are to undergo rapid two-stage ASO. We successfully used levosimendan and continuous positive airway pressure after 1st stage operation in a patient with dTGA and regressed ventricle, which helped in left ventricular preparedness, and the child underwent rapid two-stage ASO uneventfully.
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Conscious sedation for balloon mitral valvotomy: A comparison of fentanyl versus sufentanil
Annals of Cardiac Anaesthesia 2017 20(2):163-168
Context: Analgesia and sedation are required for the comfort of patient and the cardiologist during balloon mitral valvotomy. Aims: In this study, efficacy of analgesia, sedation, and patient satisfaction with sufentanil was compared with fentanyl. Settings and Design: Single-centered, prospective single-blind study of sixty patients. Materials and Methods: Patients between 15 and 45 years of rheumatic mitral stenosis with valve area of 0.8–1 cm2 undergoing elective balloon mitral valvotomy, randomly divided to receive bolus injection fentanyl 1 mcg/kg (Group 1, n = 30) followed by infusion at 1 mcg/kg/h or bolus of injection sufentanil 0.1 mcg/kg (Group 2, n = 30) followed by continuous infusion at 0.1 mcg/h. Both the groups received injection midazolam bolus 0.02 mg/kg followed by infusion at 15 mcg/kg/h. Pain intensity (by visual analog score [VAS]), level of sedation (by Ramsay sedation scale), overall patient and operator's satisfaction, effect on cardiorespiratory parameters, and discharge score (by modified Aldrete score) were assessed. Statistical Analysis Used: Statistical analysis used Student's unpaired t-test and Chi-square test. P < 0.05 was considered statistically significant. Results: Mean number of bolus doses in fentanyl group was 0.9 versus 0.13 in sufentanil group (P < 0.01). The mean value of mean blood pressure in fentanyl group was 83.52 mmHg versus 88 mmHg in sufentanil group (P < 0.05), but the value was within normal range in both the groups. The mean VAS – patient's opinion in fentanyl group was 8.97 versus 9.53 in sufentanil group (P < 0.05). Mean discharge score in fentanyl group was 17.87 versus 18.23 in sufentanil group (P < 0.05). No statistically significant difference was found with respect to heart rate, respiratory rate, oxygen saturation, PaCO2values, and anxiety scores. Conclusion: Sufentanil was found to be better with respect to analgesia, patient satisfaction, and recovery however not cost-effective for continuous infusion technique.
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Role of MicroRNA in cardiac anesthesia: An innovative consequences and new possibility
Annals of Cardiac Anaesthesia 2017 20(2):274-275
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Serial semi-invasive hemodynamic assessment following pericardiectomy for chronic constrictive pericarditis
Annals of Cardiac Anaesthesia 2017 20(2):169-177
Objectives: This study was designed to prospectively investigate the effects of pericardiectomy via median sternotomy on intra- and postoperative hemodynamics by a new semi-invasive device (Flotrac/VigileoTM monitor) using arterial pressure waveform analysis. Patients and Methods: Thirty consecutive patients aged 15 to 55 years (mean+SD, 31.73 + 13.53 years), who had undergone total pericardiectomy via median sternotomy underwent serial hemodynamic evaluation. FlotracTM Sensor – derived stroke volume, stroke volume variation, systemic vascular resistance index (SVRI), cardiac index and right atrial pressure were measured just before and after pericardiectomy, at 12 hours, 24 hours, 48 hours, 72 hours and at discharge postoperatively. Results: Majority of patients (73.33%) exhibited statistically significant reduction of right atrial pressure and SVRI along with improvement in cardiac index and oxygen delivery in the immediate and late postoperative period. However, the stroke volume and stroke volume variation did not increase proportionately on completion of surgery. Patients with low cardiac output syndrome exhibited persistently high central venous pressure with reduced cardiac index and echocardiographically abnormal diastolic filling characteristics. Conclusions: We conclude that there is early normalization of hemodynamics following pericardiectomy via median sternotomy and the adequacy of pericardiectomy can be accurately assessed by the new semi-invasive arterial pressure waveform analysis device. Stroke volume variation is a non-predictor of fluid requirement during and after pericardiectomy.
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Erratum: Annals of Cardiac Anesthesia: Beacon journey toward excellence: 2015–2017
Annals of Cardiac Anaesthesia 2017 20(2):280-280
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Methylene blue for postcardiopulmonary bypass vasoplegic syndrome: A cohort study
Annals of Cardiac Anaesthesia 2017 20(2):178-181
Background: Methylene blue (MB) has been used to treat refractory hypotension in a variety of settings. Aims: We sought to determine whether MB improved blood pressure in postcardiopulmonary bypass (CPB) vasoplegic syndrome (VS) in a complex cardiac surgery population. Furthermore, to determine variables that predicted response to MB. Setting and Design: This was conducted in a tertiary care medical center; this study was a retrospective cohort study. Materials and Methods: Adult cardiac surgery patients who received MB for post-CPB VS over a 2-year period were studied. Mean arterial blood pressure (MAP) and vasopressor doses were compared before and after MB, and logistic regression was used to model which variables predicted response. Results: Eighty-eight patients received MB for post-CPB VS during the study period. MB administration was associated with an 8 mmHg increase in MAP (P = 0.004), and peak response occurred at 2 h. Variables that were associated with a positive drug response were deep hypothermic circulatory arrest during surgery and higher MAP at the time of drug administration (P = 0.006 and 0.02). A positive response had no correlation with in-hospital mortality (P = 0.09). Conclusions: MB modestly increases MAP in cardiac surgery patients with VS. Higher MAP at the time of drug administration and surgery with deep hypothermic circulatory arrest predict a greater drug response.
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Perioperative chemotherapy versus postoperative chemoradiotherapy in patients with resectable gastric/gastroesophageal junction adenocarcinomas: A survival analysis of 5058 patients
BACKGROUND
Both perioperative chemotherapy (PECT) and postoperative chemoradiotherapy (POCRT) have a significant survival advantage over surgery alone for the treatment of patients with gastric cancer. However, to the best of our knowledge, these regimens have not been compared in a randomized clinical trial. The purpose of the current observational study was to compare overall survival among patients receiving PECT versus POCRT for the treatment of gastric/gastroesophageal junction (GEJ) adenocarcinomas.
METHODS
Patients with resected clinical American Joint Committee on Cancer TNM stage II or III adenocarcinomas of the stomach or GEJ from 2004 through 2013 were identified utilizing the National Cancer Data Base. Hazard ratios (HRs), 95% confidence intervals, and P values were computed using a Cox proportional hazards procedure. Multivariable models were adjusted for treatment regimen, age, race, ethnicity, tumor size, TNM stage, Charlson comorbidity index, and tumor grade.
RESULTS
Patients receiving PECT had a 72% survival advantage compared with those treated with POCRT (5058 patients; HR, 0.58 [adjusted P<.0001]). The 5-year actuarial survival rate for PECT was 44% compared with 38% for POCRT. A statistically significant survival advantage for PECT also was observed when the analysis was stratified by clinical stage of disease (stage II [3192 patients]: adjusted HR, 0.79 [P = .041]; and stage III [1866 patients]: adjusted HR, 0.49 [P<.0001]). This benefit was greatest among patients with lymph node-positive disease who converted to lymph node-negative status with PECT.
CONCLUSIONS
In this large series of patients with stage II/III resected gastric/GEJ adenocarcinomas from >1500 American College of Surgeons Commission on Cancer-accredited facilities, patients receiving PECT were shown to survive longer than those receiving POCRT. Cancer 2017. © 2017 American Cancer Society.
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Postmastectomy radiation therapy for breast cancer patients with one to three positive lymph nodes: a propensity score matching analysis
Future Oncology Ahead of Print.
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Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer
Abstract
Oral mucositis (OM) is a common acute side effect during radiotherapy treatments for head and neck cancer (HNC), with a potential impact on patient's compliance to therapy, quality of life (QoL) and clinical outcomes. Its timely and appropriate management is of paramount importance. Several quantitative scoring scales are available to properly assess OM and its influence on patient-reported outcomes (PROs) and QoL. We prospectively assessed OM in a cohort of HNC patients submitted to radiation using the Oral Mucositis Assessment Scale (OMAS), while its impact on PROs and QoL was evaluated employing the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN) and the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-HN). Evaluation of OMAS scores highlighted a progressive increase in OM during treatment and a partial recovery after the end of radiation. These trends were correlated to PROs and QoL as evaluated with OMWQ-HN and FACT-HN questionnaires. In the present study, we provided a quantitative assessment of OM, PROs and QoL in HNC patient undergoing radiotherapy, potentially useful for future comparison.
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Open and endovascular elective treatment of abdominal aortic aneurysms: a real-world experience
Abstract
Purpose
To present a real-world experience of the elective treatment of abdominal aortic aneurysms (AAAs) using both open repair (OR) and endovascular repair (EVAR).
Methods
Data from patients treated consecutively between January 1, 2000 and December 31, 2014 were collected retrospectively and reviewed. The primary outcomes were 30-day mortality and complication rates, freedom from reintervention, and survival in the long-term.
Results
We analyzed data on 1112 patients (660 EVAR, 452 OR). The 30-day mortality and complications rates were higher after OR than after EVAR (2.9 vs. 1.1%, P = .03 and 24.7 vs. 1.1%, P < .0001, respectively). At 10 years, survival was 66.1 ± 3.2% after OR and 78.1 ± 2.2% after EVAR (P = .0006) and freedom from reintervention was 93.5 ± 1.8% after OR and 88.4 ± 1.8% after EVAR (P = .005). The preoperative aneurysm diameter was significantly associated with the development of type Ia endoleaks after EVAR (P < .0001) and of a proximal pseudoaneurysm after OR (P < .0001).
Conclusion
In the long-term, EVAR was associated with higher reintervention rates, but better survival than OR. The preoperative AAA diameter was the most important predictor of the development of endoleaks after EVAR and proximal pseudoaneurysm after OR.
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Hospital cost savings and other advantages of sutureless vs stented aortic valves for intermediate-risk elderly patients
Abstract
Purpose
To evaluate and compare the clinical outcomes and hospital costs of using sutureless aortic valves vs conventional stented aortic valves.
Methods
Between 2007 and 2011, 52 elderly patients undergoing aortic valve replacement for aortic stenosis in our center had a sutureless valve inserted. From among 180 patients who had a stented valve inserted during the same period, 52 patients were matched to the sutureless group, based on age, gender, and operation type. We compared clinical outcomes and hospital costs between the two groups.
Results
The sutureless group had a higher Euroscore (logistic Euroscore I) risk (12.8 vs 9.7; p = 0.02), with significantly shorter aortic cross-clamp (ACC) time (p < 0.01), cardiopulmonary bypass (CPB) time (p < 0.01), intensive care unit stay (p < 0.01), intubation time (p < 0.01), and overall hospital stay (p = 0.05). The sutureless group also revealed a significant hospital cost saving of approximately 8200€ (p = 0.01).
Conclusions
The clinical and hemodynamic outcomes of using the sutureless bioprosthesis were excellent. The reduced ACC and CPB times had a favorable effect on the duration of intubation and intensive care stay, resulting not only in faster recovery and discharge home, but also in a significant hospital cost reduction.
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Safety and feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy for esophageal cancer
Abstract
Purpose
Neoadjuvant chemotherapy (NAC) with cisplatin and fluorouracil is the recommended standard treatment for resectable locally advanced esophageal cancer (EC) in Japan. We investigated the effects of NAC on the safety and feasibility of thoracoscopic esophagectomy with total mediastinal lymphadenectomy for EC.
Methods
This retrospective study analyzed data from 225 consecutive patients who underwent thoracoscopic esophagectomy with lymph node dissection between April 2007 and December 2015. Patients with clinical stage IB, IIA, IIB, IIIA, or IIIB EC, and no active concomitant malignancy were included. We compared intraoperative outcomes, and postoperative morbidity and mortality between patients who received NAC (n = 139; NAC group) and patients who did not (n = 86; non-NAC group).
Results
Preoperative laboratory data revealed that anemia, thrombopenia, and renal dysfunction were more common in the NAC group than in the non-NAC group. There were no differences between the groups in operating times, blood loss, number of dissected lymph nodes, overall complication rates, or length of postoperative hospital stay.
Conclusion
Based on our findings, thoracoscopic esophagectomy is safe and effective for locally advanced EC, even after NAC.
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Acute aortic valvular regurgitation with pulmonary haemorrhage in Wegener's granulomatosis presenting as dyspnoea: a rare presentation
Mani Nallasivan<br />Dec 6, 2010; 2010:bcr1120092474-bcr1120092474<br />case-report
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Paediatric magnetic resonance enteroclysis under general anaesthesia – initial experience
Abstract
MR enterography is the accepted imaging reference standard for small bowel assessment in inflammatory bowel disease. There is an increasing cohort of children with inflammatory bowel disease presenting at an early age (<5 years) with severe disease. Younger children present a technical challenge for enterography because of the need for sedation/general anaesthesia to allow image optimisation and the need for oral contrast to allow adequate luminal assessment. Through our experiences, MR enteroclysis under general anaesthesia has proven to be a successful imaging technique for the work-up of these patients. In this paper, we present our institutional practice for performing MR enteroclysis under general anaesthesia.
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Researchers Design a Precise Library for CRISPR-Mediated Genetic Screens
Researchers in the Cancer Target Discovery and Development Network used machine learning to create improved CRISPR libraries for genomic studies. Their new libraries of single guide RNAs can be used to alter gene expression with greater sensitivity and specificity.
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Longitudinal Decline of Striatal Subregional [ 18 F]FP-CIT Uptake in Parkinson’s Disease
Abstract
Purpose
Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects. We investigated the longitudinal decline characteristics of striatal [18F]FP-CIT uptake in PD.
Methods
We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [18F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.
Results
Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.
Conclusions
The longitudinal decline of striatal [18F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.
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Importance of relying on examples for both anesthesiologists and other physicians to assign unbiased American Society of Anesthesiologists Physical Status Classifications
In this month's issue of the Journal of Clinical Anesthesia, Curatolo and colleagues compare American Society of Anesthesiologists' Physical Status (ASA PS) scoring by anesthesiologists and internal medicine physicians [1]. Using 20 cases (scenarios), they showed that internists assigned significantly lower ASA PS scores than did anesthesiologists [1]. The internists "had a 30–40% chance of under-rating the ASA PS of the patients in the clinical vignettes" compared with the anesthesiologists [1].
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Less postoperative sore throat after nasotracheal intubation using a fiberoptic bronchoscope than using a Macintosh laryngoscope: A double-blind, randomized, controlled study
To evaluate whether nasotracheal intubation using a fiberoptic bronchoscope reduces postoperative sore throat.
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Determining predictive value of preoperative tests for difficult intubation
In the recent article by Mahmoodpoor et al. [1] evaluating the predictive value of several preoperative tests for difficult intubation in a prospective descriptive study, they conclude that facial angle has a high sensitivity, positive and negative predictive value, and Youden index for prediction of difficult intubation, but the best result is achieved when facial angle is used in combination with either the modified Mallampati score or upper lip bit test. As difficult intubation prediction by preoperative tests is a crucial component of safe airway management algorithm [2], their findings have potential implications.
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Malignancy in Pheochromocytoma or Paraganglioma: Integrative Analysis of 176 Cases in TCGA
Abstract
Methods of diagnosing malignant pheochromocytoma (PCC) or paraganglioma (PGL) are needed. However, there are no reliable histopathologic criteria to distinguish malignant PCC/PGLs. The recent genomic analysis of The Cancer Genome Atlas (TCGA) provides in-depth information enabling more accurate diagnosis of disease entities. Therefore, we investigated genomic expression differences and mutational differences of malignant PCC/PGLs with TCGA. As of December 2014, TCGA had acquired multigenomic analysis of 176 PCC/PGL samples. Clinical information, mutation status, and 20,531 gene messenger RNA (mRNA) expression dataset of normalized RNA-sequencing mRNA read counts were downloaded from TCGA, and integrated into a table. Of the 176 PCC/PGL samples in the dataset, 14 had metastasis and 162 exhibited no metastasis. mRNA expression and mutations were compared in these two groups. There were 76 males in the dataset of 176 TCGA samples. Mean age was 47.6 ± 15.2 years (19–83 years). There was no significant gender or race difference between metastatic and non-metastatic groups. mRNA expression of malignant PCC/PGLs was upregulated in five pathways of cell cycle (BUB1, BUB1B, CCNB2, CDC2, ESPL1), calcium signaling (CCNB2, CDC2, PRKCB1), regulation of actin cytoskeleton (DIAPH3, FGF18, IQGAP3), gap junction (CDC2, PRKCB1), and phosphatidylinositol (PRKCB1, TTK). Disease-free survival rates were significantly correlated with the presence or absence of mutations, such as RP11-798G7.5, HERC2, SETD2, TGDS, TRHDE, FKBP9, and BMS1. TCGA showed differences in mRNA expression and mutations between metastatic and non-metastatic PCC/PGLs. The improved recognition of genetic causes can help to achieve proper diagnosis and provide appropriate treatment of PCC/PGL.
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Functional outcome after surgery in patients with bone sarcoma around the knee; results from a long-term prospective study
Background and Objectives
In a previous conducted study functional outcome of young patients with bone sarcoma located around the knee was longitudinally evaluated during the first 2 years postoperatively. Functional outcome improved significantly over the first 2 years. The purpose of this descriptive study was to evaluate the functional outcome of these patients at long-term follow-up of 7 years.
Methods
Functional outcome was assessed with the TESS, MSTS, Baecke questionnaire, and three functional performance tests: time up and down stairs (TUDS), various walking activities (VWA), and the 6-min walking test (6MWT). Linear Mixed Model has been employed for the repeated measurements.
Results
Twenty patients of the original study (n = 44) participated in the current study. Fifteen limb-salvage and five ablative surgery patients, median follow-up 7.4 years (6.8-8.0) (CI 95%), mean age 22.3 years (18.2-31.6). Between 2 and 7 years after surgery, 8 limb-salvage patients (53%) encountered surgery related complications. Questionnaires and functional performance tests showed no significant difference in functional outcome between 2 years and 7 years after surgery (P < 0.05).
Conclusions
Between 2 years and follow-up at average 7 years after surgery no further improvements were noticed at young patients with a bone sarcoma located around the knee.
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Risk factors for anastomotic leakage following esophagectomy: Impact of thoracic epidural analgesia
Background and Objectives
Anastomotic leakage (AL) is one of common complications after esophageal cancer surgery. Thoracic epidural analgesia (TEA) is often recommended in patients undergoing esophagectomy. However, the impact of TEA on AL is still controversial. Thus, we conducted this study to evaluate the effect of TEA on the occurrence of AL and identify risk factors for the development of AL following esophagectomy.
Methods
Our retrospective study identified patients who underwent elective esophagectomy between July 2013 and July 2016. Univariate and multivariate logistics analyses and propensity score matching analysis were conducted to identify the risk factors for AL occurring within 30 days after operation.
Results
Overall 30-day AL was 7.9%. Multivariate analysis revealed that surgical procedure (Sweet: referent; Ivor-Lewis: OR 2.854; 95%CI 1.726-4.718; Three-incision: OR 4.837; 95%CI 3.457-6.768) and surgeon (high-volume: referent; low-volume: OR 1.740; 95%CI 1.269-2.384) were independent risk factors for AL after esophagectomy. No statistically significant difference was observed in the incidences of AL between the epidural analgesia group and the intravenous analgesia group either before or after propensity score matching (9.1% vs 7.7%, P = 0.359; 8.3% vs 9.2%, P = 0.683).
Conclusions
TEA does not affect the AL risk after esophagectomy.
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PanIN Neuroendocrine Cells Promote Tumorigenesis via Neuronal Cross-talk
Nerves are a notable feature of the tumor microenvironment in some epithelial tumors, but their role in the malignant progression of pancreatic ductal adenocarcinoma (PDAC) is uncertain. Here, we identify dense innervation in the microenvironment of precancerous pancreatic lesions, known as pancreatic intraepithelial neoplasms (PanIN), and describe a unique subpopulation of neuroendocrine PanIN cells that express the neuropeptide substance P (SP) receptor neurokinin 1-R (NK1-R). Using organoid culture, we demonstrated that sensory neurons promoted the proliferation of PanIN organoids via SP-NK1-R signaling and STAT3 activation. Nerve-responsive neuroendocrine cells exerted trophic influences and potentiated global PanIN organoid growth. Sensory denervation of a genetically engineered mouse model of PDAC led to loss of STAT3 activation, a decrease in the neoplastic neuroendocrine cell population, and impaired PanIN progression to tumor. Overall, our data provide evidence that nerves of the PanIN microenvironment promote oncogenesis, likely via direct signaling to neoplastic neuroendocrine cells capable of trophic influences. These findings identify neuroepithelial cross-talk as a potential novel target in PDAC treatment. Cancer Res; 77(8); 1–12. ©2017 AACR.
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Multinuclear NMR and MRI reveal an early metabolic response to mTOR inhibition in sarcoma
Biomarkers predicting rapalog responses in sarcomas where PI3K and mTOR are often hyperactivated could improve the suitable recruitment of responsive patients to clinical trials. PI3K/mTOR pathway activation drives energy production by regulating anaerobic glycolysis in cancer cells, suggesting a route toward a monitoring strategy. In this study, we took a multi-modality approach to evaluate the phenotypic effects and metabolic changes which occur with inhibition of the PI3K/mTOR pathway. Its central role in regulating glycolysis in human sarcomas was evaluated by short- and long-term rapamycin treatment in sarcoma cell lines. We observed an overall decrease in lactate production in vitro followed by cell growth inhibition. In vivo we observed a similar quantitative reduction in lactate production as monitored by hyperpolarized MRI, also followed by tumor size changes. This non-invasive imaging method could distinguish reduced cell proliferation from induction of cell death. Our resuits illustrate the use of hyperpolarized MRI as a sensitive technique to monitor drug-induced perturbation of the PI3K/mTOR pathway in sarcomas.
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Spermidine prolongs lifespan and prevents liver fibrosis and hepatocellular carcinoma by activating MAP1S-mediated autophagy
Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy which trigger oxidative stress-induced cell death and promote liver fibrosis and HCC. We found that the autophagic marker protein LC3 interacted with the microtubule-associated protein MAP1S which positively regulated autophagy flux in cells. MAP1S stability was regulated in turn by its interaction with the histone deacetylase HDAC4. Notably, MAP1S-deficient mice exhibited a 20% reduction in median survival and developed severe liver fibrosis and HCC under stress. Wild-type mice or cells treated with spermidine exhibited a relative increase in MAP1S stability and autophagy signaling via depletion of cytosolic HDAC4. Extending recent evidence that orally administered spermidine can extend lifespan in mice, we determined that life extension of up to 25% can be produced by lifelong administration which also reduced liver fibrosis and HCC foci as induced by chemical insults. Genetic investigations established that these observed impacts of oral spermidine administration relied upon MAP1S-mediated autophagy. Our findings offer a preclinical proof of concept for the administration of oral spermidine to prevent liver fibrosis and HCC and potentially extend lifespan.
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Genome analysis of Heliothis virescens ascovirus 3h isolated from China
Abstract
No ascovirus isolated from China has been sequenced so far. Therefore, in this study, we aimed to sequence the genome of Heliothis virescens ascovirus 3h (HvAV-3h) using the 454 pyrosequencing technology. The genome was found to be 190,519-bp long with a G+C content of 45.5%. We also found that it encodes 185 hypothetical open reading frames (ORFs) along with at least 50 amino acids, including 181 ORFs found in other ascoviruses and 4 unique ORFs. Gene-parity plots and phylogenetic analysis revealed a close relationship between HvAV-3h and three other HvAV-3a strains and a distant relationship with Spodoptera frugiperda ascovirus 1a (SfAV-1a), Trichoplusia ni ascovirus 6a (TnAV-6a), and Diadromus pulchellus ascovirus 4a (DpAV-4a). Among the 185 potential genes encoded by the genome, 44 core genes were found in all the sequenced ascoviruses. In addition, 25 genes were found to be conserved in all ascoviruses except DpAV-4a. In the HvAV-3h genome, 24 baculovirus repeat ORFs (bros) were present, and the typical homologous repeat regions (hrs) were absent. This study supplies information important for understanding the conservation and functions of ascovirus genes as well as the variety of ascoviral genomes.
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Endovascular recanalisation of a chronic occlusion of the retrohepatic IVC associated to a filter in a patient with antiphospholipid syndrome
Inferior vena cava (IVC) filters are useful adjuncts to prevent venous thromboembolism to the pulmonary circulation in the setting of contraindication for anticoagulation. Despite their proven decreased rate of pulmonary embolism, IVC filters are not without complications. We herein present the case of a 22-year-old man with a history of antiphospholipid antibody syndrome who was sent to our institution for evaluation with Budd-Chiari and post-thrombotic syndromes associated to a chronic retrohepatic complete IVC occlusion secondary to an IVC filter placed 5 years earlier. Via common femoral, transjugular and transhepatic accesses, we performed a successful endovascular recanalisation and reconstruction of the IVC with a 16 mmx60 mm covered stent; the hepatic outflow was restored with an 8x20 mm Palmaz stent. At 12-month follow-up, his symptoms have resolved, and his liver tests are within normal limits. He remains on systemic anticoagulation.
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Isolated brachydactyly type E and idiopathic pancreatitis in a patient presenting to a lipid disorders clinic
An 18-year-old female tertiary student was referred to a lipid clinic with hypertriglyceridaemia discovered after presentation with acute pancreatitis. The patient's only medication was l-thyroxine for treatment of hypothyroidism. She was overweight, normotensive, with unremarkable facies. However, she had hypermobile hand joints and brachydactyly resulting in loss of left 3–5 and right 4 and 5 knuckle definitions. Radiography revealed shortening of metacarpals 3–5 on the left and 4 and 5 on the right. Her mother had similar skeletal changes, consistent with a dominant mode of inheritance. Abnormally short digits involving the metacarpals, classified as brachydactyly type E, can be isolated or occur as part of a syndrome. Turner syndrome, Albright hereditary osteodystrophy, hypertension with brachydactyly, chromosome 2q37 microdeletion and PTHLH mutations were excluded following clinical, biochemical and genetic testing. No specific treatment was required. Genetic testing for isolated and syndromic forms of brachydactyly facilitates family screening and prepregnancy counselling.
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Delayed presentation of button battery ingestion: a devastating complication
A 12-month-old child presented with a prolonged history of fever, cough and difficulty breathing, which was initially treated as bronchiolitis. She was discharged but presented again to Accident and Emergency department 4 days later with worsening symptom. Following deterioration in the Emergency department, a chest X-ray revealed a button battery in the upper oesophagus. Emergency oesophagoscopy was performed where a 20 mm button battery was removed and a tracheoesophageal fistula was seen 12 mm above the carina. Near total oesophagectomy, cervical oesophagostomy and gastrostomy were performed with a patch repair of the trachea, followed by a bioabsorbable tracheal stent. The patient spent a prolonged period of time in intensive care and was treated with intravenous antibiotics for mediastinitis. This case highlights the difficulty in diagnosis of button batteries when there is no clear history and the devastating consequences of prolonged exposure.
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Circulating tumor cells and coagulation − minireview
Source:Critical Reviews in Oncology/Hematology
Author(s): Branislav Bystricky, James M. Reuben, Michal Mego
Venous thromboembolic events in cancer patients signify poor prognosis. Prophylactic treatment of ambulatory patients with anticoagulants is currently not recommended. Circulating tumor cells, either directly or indirectly, are associated with prothrombotic state. In this review, we discuss various interactions of circulating tumor cells with the coagulation pathway in cancer patient.
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Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance, and recovery in patients with non-small cell lung cancer: a systematic review
Source:Critical Reviews in Oncology/Hematology
Author(s): Elisabeth J. Driessen, Marieke E. Peeters, Bart C. Bongers, Huub A. Maas, Gerbern P. Bootsma, Nico L. van Meeteren, Maryska L. Janssen-Heijnen
This systematic review aimed to examine physical fitness, adherence, treatment tolerance, and recovery for (p)rehabilitation including a home-based component for patients with non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. Studies describing (home-based) prehabilitation or rehabilitation in patients with NSCLC were included from four databases (January 2000-April 2016, N=11). Nine of ten rehabilitation studies and one prehabilitation study (437 NSCLC patients, mean age 59-72 years) showed significantly or clinically relevant improved physical fitness. Three (27%) assessed home-based training and eight (73%) combined training at home, inhospital (intramural) and/or at the physiotherapy practice/department (extramural). Six (55%) applied supervision of home-based components, and four (36%) a personalized training program. Adherence varied strongly (9-125% for exercises, 50-100% for patients). Treatment tolerance and recovery were heterogeneously reported. Although promising results of (p)rehabilitation for improving physical fitness were found (especially in case of supervision and personalization), adequately powered studies for home-based (p)rehabilitation are needed.
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Analgesia and side effects of the addition of 10 or 20 µg fentanyl to articaine in spinal anesthesia for knee arthroscopy: a randomized and observer-blinded study
Abstract
Objectives
Articaine, a popular and rapidly acting local anesthetic in dentistry, has been also found to be beneficial in ambulatory spinal anesthesia. Analgesia in the intraoperative and immediate postoperative period may be further improved by adding fentanyl to the local anesthetic solution for spinal anesthesia. The aim was to evaluate dose-dependency of analgesia and side effects associated with intrathecal fentanyl additive to articaine for spinal anesthesia in knee arthroscopy patients.
Methods
In this randomized, observer- and patient-blinded study, 90 adult patients scheduled for elective ambulatory knee arthroscopy under spinal anesthesia were randomized into three groups: plain articaine 60 mg with saline (group AF0), articaine 60 mg with fentanyl 10 µg (group AF10) or 20 µg (group AF20) in a total volume of 1.9 ml. The blinded observer tested the sensory and the motor block, and performed telephone interviews on the first and seventh postoperative days.
Results
The median (IQR) duration of sensory block at the dermatomal level of T10 was significantly longer in groups AF10, 69 min (56) and AF20, 69 min (45) than in group AF0, 41 min (35) (p = 0.013). Motor block duration was similar in all groups (median 120 min). Group AF20 patients experienced pruritus significantly more often than patients in the other groups (p = 0.039). No acute or late anesthetic side effects occurred, and satisfaction with the anesthetic technique was the same in all groups (97% satisfied).
Conclusions
Fentanyl 10 or 20 µg as additive to articaine for spinal anesthesia prolonged the duration of sensory block significantly and similarly. Fentanyl 20 µg was more often associated with pruritus than fentanyl 10 µg.
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Socioeconomic factors and survival in patients with non-metastatic head and neck squamous cell carcinoma
Summary
The effect of socioeconomic factors on receipt of definitive treatment and survival outcomes in non-metastatic head and neck squamous cell carcinoma (HNSCC) remains unclear. Eligible patients (n = 37,995) were identified from the United States Surveillance, Epidemiology and End Results (SEER) database between 2007 and 2012. Socioeconomic factors (i.e., median household income, education level, unemployment rate, insurance status, marital status and residence) were included in univariate/multivariate Cox regression analysis; validated factors were used to generate nomograms for cause-specific survival (CSS) and overall survival (OS), and a prognostic score model for risk stratification. Low- and high-risk groups were compared for all cancer subsites. Impact of race/ethnicity on survival was investigated in each risk group. Marital status, median household income and insurance status were included in the nomograms for CSS and OS, which had higher c-indexes than the 6th edition TNM staging system (all P-values < 0.001). Based on three disadvantageous socioeconomic factors (i.e., unmarried status, uninsured status, median household income < US $65,394), the prognostic score model generated four risk subgroups with scores of 0, 1, 2 or 3, which had significantly separated CSS/OS curves (all P-values < 0.001). Low-risk patients (score 0-1) were more likely to receive definitive treatment and obtain better CSS/OS than high-risk patients (score 2-3). Chinese and non-Hispanic black patients with high-risk socioeconomic status had best and poorest CSS/OS, respectively. Therefore, marital status, median household income and insurance status have significance for predicting survival outcomes. Low-risk socioeconomic status and Chinese race/ethnicity confer protective effects in HNSCC.
This article is protected by copyright. All rights reserved.
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The miR-200b–ZEB1 circuit regulates diverse stemness of human hepatocellular carcinoma
Abstract
Accumulating evidence suggests that human hepatocellular carcinoma (HCC) can be derived from cancer stem cells (CSCs), which contribute to tumor initiation, metastasis, chemoresistance, and recurrence. A great variety of HCC CSCs resulting in diverse clinical manifestations have been reported. However, how CSC diversity is regulated and generated remains unclear. Here we report that the miR-200b–ZEB1 circuit is closely involved with the induction and maintenance of a diverse group of CSCs. We found that miR-200b downregulation occurred in early HCC and associated with poor prognosis. The downregulation was attributable to genome deletion and promoter methylation of the miR-200a/b/429 gene. Ectopic expression of miR-200b or silencing of ZEB1 led to a decrease in CD13+ and CD24+ HCC CSCs and an increase in EpCAM+ HCC CSCs. Mechanistically, miR-200b directly suppressed BMI1 and ZEB1 expressions. ZEB1 recognized promoters of CD13, CD24 and EpCAM genes resulting in CD13 and CD24 upregulation and EpCAM downregulation. Neither miR-200b nor ZEB1 had obvious effects on CD133 or CD90 expression. Silencing CD13 or CD24 expression suppressed tumorigenicity of HCC cells. Ectopic expression of CD24 reversed the suppression of tumorigenicity by ectopic expression of miR-200b. Clinically, miR-200b downregulation was coupled with ZEB1 upregulation in approximately two-thirds of HCC patients. ZEB1 expression was positively correlated with CD13 and CD24 expressions in HCCs, while miR-200b expression was positively correlated with EpCAM. Our findings suggest that the miR-200b–ZEB1 circuit is a master regulator of diverse stemness of HCC, which differentiates HCCs into those containing CD13+/CD24+ CSCs from those containing EpCAM+ CSCs. This article is protected by copyright. All rights reserved
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Upregulated miR-132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway
Abstract
Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5+ cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens. By comparing the miRNA expression profiles of Lgr5+ GCSCs and Lrg5- cells, we established the upregulation of miR-132 in Lgr5+ GCSCs. The enhanced miR-132 expression correlated chemo-resistance in GC patients. Kaplan–Meier survival curve showed that patients with low miR-132 expression survived obviously longer. Functional assays results indicated that miR-132 promoted cisplatin resistance in Lgr5+ GCSCs in vitro and in vivo. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-132. The expression of miR-132 was inversely correlated with SIRT1 in gastric cancer specimens. Furthermore, through PCR array we discovered ABCG2 was one of the downstream targets of SIRT1. Overexpression of SIRT1 down-regulated ABCG2 expression by promoting the de-acetylation of the transcription factor CREB. CREB was further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Thus, we concluded that miR-132 regulated SIRT1/CREB/ABCG2 signaling pathway contributing to the cisplatin resistance and might serve as a novel therapeutic target against gastric cancer. This article is protected by copyright. All rights reserved
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Patterns of Care for Patients with Early-Stage Glottic Cancer Undergoing Definitive Radiotherapy: A National Cancer Database Analysis
Publication date: Available online 6 April 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): William A. Stokes, Diana Abbott, Andy Phan, David Raben, Ryan M. Lanning, Sana D. Karam
PurposeTo characterize practice patterns, including temporal trends, in fractionation schedules among patients in the United States undergoing definitive radiotherapy for early-stage glottic cancer and to compare overall survival outcomes between fractionation schedules.Methods and MaterialsWe queried the National Cancer Database for patients with TisN0M0, T1N0M0, or T2N0M0 squamous cell carcinoma of the glottic larynx diagnosed between 2004 and 2012 and undergoing definitive radiotherapy. Dose per fraction was calculated to define cohorts undergoing conventional fractionation (CFxn) and hypofractionation (HFxn). Logistic regression was performed to identify predictors of receiving HFxn, and Cox regression was used to determine predictors of mortality. One-to-one propensity-score matching (PSM) was then employed to compare survival between fractionation schedules.Results10,539 patients were included, with 6,576 undergoing CFxn and 3,963 undergoing HFxn. T1 patients comprised a majority of each cohort. Use of HFxn increased significantly over the period studied (p<0.001), but even in the final year nearly one half of patients continued to receive CFxn. Receipt of HFxn was also independently associated with higher income and facility types other than community cancer program on logistic regression. On multivariate Cox regression, HFxn was associated with improved survival (hazard ratio [HR] for death 0.90, 95% confidence interval [95%CI] 0.83-0.97, p=0.008), a finding redemonstrated on univariate Cox regression among a well-matched PSM cohort (HR 0.88, 95%CI 0.80-0.96, p=0.003). Subgroup Cox multivariate analysis demonstrated a significant survival advantage with HFxn among T1 patients (HR 0.90, 95%CI 0.81-0.99; p=0.042), but a nonsignificant benefit among those with Tis (HR 0.86, 95%CI 0.57-1.30; p=0.472) or T2 disease (HR 0.88, 95%CI 0.76-1.02; p=0.099).ConclusionsUtilization of HFxn is increasing and is associated with improved survival over CFxn. Our findings support the broadened use of HFxn for patients with early-stage glottic cancer undergoing definitive radiotherapy.
Teaser
While a 2006 Japanese trial demonstrated that patients undergoing definitive radiotherapy for early-stage glottic larynx cancer derive a local control benefit from hypofractionation, it is unclear how its publication has influenced fractionation patterns in the US or whether hypofractionation translates to a survival advantage. In an analysis of care patterns and outcomes in the National Cancer Database, we identified both increased use of hypofractionation after 2006 through 2012 and improved overall survival with this approach.from Cancer via ola Kala on Inoreader http://ift.tt/2nOevb6
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The epidemiology of sickle cell disease in Germany following recent large-scale immigration
Abstract
Background
The epidemiology of sickle cell disease (SCD) in Germany is currently changing fundamentally with ongoing immigration. Here, we address the challenges resulting from the increased frequency, that is, the morbidity, and mortality of SCD in this population.
Procedure
The number of immigrants with SCD was estimated based on the data of the German central registry of migrants (2007–2015) and published epidemiologic data. Additional data analysis was based on nationwide aggregated data from the diagnosis-related groups' (DRG) statistics of the German Federal Statistical Office.
Results
The total number of patients with SCD among migrants was estimated at 2,016 in 2007 and 3,216 in 2015, thus showing a 60% increase, which was particularly remarkable during 2014 and 2015. The countries of origin included those of West sub-Saharan Africa, followed by Syria, and other countries of the Middle East. In parallel, the number of SCD inpatient treatments increased from 780 in 2002 to 1,340 in 2015. Between 2012 and 2014, 42 patients with SCD died in hospital, mostly at an age of less than 5 years (n = 7) or over 30 years (n = 29).
Conclusion
More than 3,000 patients with SCD are estimated to live among the immigrant population in Germany. In addition, the number of SCD patients of German nationality is not known. The increasing number of inpatient treatments and the death of young children from SCD indicate the need for a general newborn screening program and an increased awareness of this disease among medical practitioners in a country in which SCD used to be rare.
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Nephrogenic rests in Wilms tumors treated with preoperative chemotherapy: The UK SIOP Wilms Tumor 2001 Trial experience
Abstract
Background
Nephrogenic rests (NRs) are abnormally persistent foci of embryonal cells, thought to be the precursor lesion of Wilms tumors (WTs). To date, their presence has not been systematically examined in WTs treated with preoperative chemotherapy.
Methods
A systematic analysis of the data on NRs in WTs treated with preoperative chemotherapy obtained from the UK cohort of the International Society of Pediatric Oncology (SIOP) WT 2001 Trial. The study was based on central pathology review of full sets of slides from pathological specimens, with a median of 28 slides reviewed per case.
Results
NRs were identified in 40% of unilateral WTs, including 25% perilobar nephrogenic rest (PLNR), 9% intralobar nephrogenic rest (ILNR), 5% both PLNR and ILNR, and 1% nephroblastomatosis, and in 93% of cases with bilateral lesions. ILNRs were associated with stromal histology and a younger age at diagnosis and found frequently in patients with congenital anomalies associated with WT1 mutation. PLNRs were found frequently in patients with overgrowth syndromes.
Conclusions
The prevalence of NRs in WTs after preoperative chemotherapy observed in SIOP UK WT 2001 Trial is similar to the previously published data on NRs not treated with preoperative chemotherapy. Their epidemiology supports at least two pathways to Wilms tumorigenesis.
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Unleashing the immune response against childhood solid cancers
Abstract
Tumor immunotherapy has come to the fore fuelled by impressive clinical responses to checkpoint inhibitor antibodies in a range of adult malignancies and by the success of chimeric antigen receptor T cells targeting adult and pediatric B-cell malignancies. Clearly, if appropriately fine-tuned, the immune system has the capability to seek out and destroy cancer. Studies in pediatric solid cancers so far have not shown the therapeutic potential checkpoint inhibitors described in adult cancers and this may reflect fewer tumor-associated antigens or different immune evasion mechanisms. One potential approach to overcome these limitations will be to combine interventions to undermine immune evasion mechanisms with engineered T-cell adoptive transfer.
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Treatment outcomes of children with Hodgkin lymphoma between 2000 and 2010: First report by the South African Children's Cancer Study Group
Abstract
Background
Children with Hodgkin lymphoma (HL) have excellent survival rates in high-income countries, but there are minimal outcome data in South African patients. Differing approaches to treatment are used in centres across South Africa, and the South African Children's Cancer Study Group (SACCSG) embarked on a programme to audit outcomes to improve survival rates.
Patients and Methods
A multicentre study was conducted to analyse outcomes and prognostic factors of children with HL in South Africa. Ten dedicated South African paediatric oncology units participated in a retrospective data review. All patients with HL treated consecutively between January 2000 and December 2010 were included. Kaplan–Meier curves and Cox regression model were employed to determine survival rates and prognostic factors.
Results
Two hundred and ninety-four patients were eligible for inclusion. The median age at presentation was 9.6 years (range 2.9–18.8); 55.4% of the patients presented with Stage III and IV disease and 9.9% were human immunodeficiency virus (HIV) positive. First-line therapy consisted of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) in 158 patients, vincristine, procarbazine/etoposide, prednisone and doxorubicin in 97 and adriamycin, bleomycin, vincristine and dacarbazine–chlorambucil, vinblastine, prednisone and procarbazine in 23 patients. The 5-year overall survival (OS) was 79% (95% confidence interval 73–84%). Multivariate analysis demonstrated that HIV infection (P = 0.018) and Ann Arbor Stage III and IV disease (P = 0.006) conferred a poor prognosis, while treatment with ABVD was associated with higher survival rates (P = 0.028).
Conclusion
OS rates are encouraging for a middle-income country, although economic disparities continue to impact negatively on outcomes. Study results will form the basis for the development of national protocol and continued advocacy to rectify disparities.
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MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group
Abstract
Background
Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma.
Procedure
Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961. Comparisons of clinical and biologic features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free (EFS) and overall (OS) survival compared using log–rank tests and modeled using Cox models.
Results
Thirty of 343 patients (8.7%) had MIBG nonavid disease. Patients with nonavid tumors were less likely to have adrenal primary tumors (34.5 vs. 57.2%; P = 0.019), bone metastases (36.7 vs. 61.7%; P = 0.008), or positive urine catecholamines (66.7 vs. 91.0%; P < 0.001) compared with patients with MIBG avid tumors. Nonavid tumors were more likely to be MYCN amplified (53.8 vs. 32.6%; P = 0.030) and had lower norepinephrine transporter expression. Patients with MIBG nonavid disease had a 5-year EFS of 50.0% compared with 38.7% for patients with MIBG avid disease (P = 0.028). On multivariate testing in high-risk patients, MIBG avidity was the sole adverse prognostic factor for EFS identified (hazard ratio 1.77; 95% confidence interval 1.04–2.99; P = 0.034).
Conclusions
Patients with MIBG nonavid neuroblastoma have lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN-amplified tumors, these patients have superior outcomes compared with patients with MIBG avid disease.
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Preparing childhood cancer survivors for transition to adult care: The young adult perspective
Abstract
Background
Childhood cancer survivors (CCSs) remain at risk for developing treatment-associated health conditions as they age; however, many do not obtain recommended follow-up, putting them at unnecessary risk for morbidity. Educational interventions targeted at providing survivors with the knowledge and skills necessary for healthcare independence might improve adherence and outcomes as they transition care to the adult medical system.
Objective
To identify informational needs, educational preferences, and support that young adult CCSs perceive as beneficial for transition from pediatric to adult medical care.
Design/Method
Sixteen young adult CCSs (ages 22–39 years) who have transitioned to adult care participated in focus groups led by a trained moderator and analyzed using a thematic analysis approach.
Results
Four major themes emerged: (1) education preferences—pediatric oncology provider as the primary source of information and guidance, enhanced by other formats, and early and ongoing engagement in education; (2) family role in transition—desire for independence and acknowledgement of need for ongoing parental support; (3) expectations for adult providers, such as close relationships, open communication, and care coordination; and (4) knowledge deficits regarding disease/treatment history, risk for long-term complications, and navigation of the adult medical system.
Conclusion
Transition education as described by young adult CCSs should be a developmentally appropriate process beginning in early adolescents, primarily administered by pediatric oncology providers, and delivered in multiple formats. While healthcare independence is a goal for young adult CCSs, all stakeholders must recognize that families and providers continue to have an important role supporting survivors with transition logistics and medical decision-making.
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Bevacizumab for malignant gliomas: current indications, mechanisms of action and resistance, and markers of response
Abstract
Vascular endothelial growth factor (VEGF) is an attractive target of antiangiogenic therapy in glioblastomas. Bevacizumab (Bev), a humanized anti-VEGF antibody, is associated with the improvement of progression-free survival and performance status in patients with glioblastoma. However, randomized trials uniformly suggest that these favorable clinical effects of Bev do not translate into an overall survival benefit. The mechanisms of action of Bev appear to include the inhibition of tumor angiogenesis, as well as indirect effects such as the depletion of niches for glioma stem cells and stimulation of antitumor immunity. Although several molecules/pathways have been reported to mediate adaptation and resistance to Bev, including the activation of alternative pro-angiogenic pathways, the resistance mechanisms have not been fully elucidated; for example, the mechanism that reinduces tumor hypoxia remains unclarified. The identification of imaging characteristics or biomarkers predicting the response to Bev, as well as the better understanding of the mechanisms of action and resistance, is crucial to improve the overall clinical outcome and optimize individual therapy. In this article, the authors review the results of important clinical trials/studies, the current understanding of the mechanisms of action and resistance, and the knowledge of imaging characteristics and biomarkers predicting the response to Bev.
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Patterns of recurrence in patients achieving pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer
Abstract
Purpose
The aim of this study was to characterize the patterns of recurrence in patients achieving pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer.
Methods
Patients with locally advanced rectal cancer treated with neoadjuvant CRT and who achieved pCR from January 2004 to December 2012 were collected. The primary outcome measurement was the patterns of recurrence.
Results
Among 195 patients who achieved pCR, 18 developed recurrence. Furthermore, local recurrence occurred in 1.5% of patients (3/195), while distant metastases occurred in 7.7% of patients (15/195), which included 7 lung metastases, 1 liver metastasis, and 8 metastases in other locations.
Conclusions
Our study indicated that patients achieving pCR following neoadjuvant CRT have a favorable prognosis, with distant metastases predominating in all recurrences. Among patients with distant metastases, non-liver metastases were the predominant pattern.
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The evolving role for re-irradiation in the management of recurrent grade 4 glioma
Abstract
Although significant gains have been realized in the management of grade 4 glioma, the majority of these patients will ultimately suffer local recurrence within the prior field of treatment. Clearly, novel local treatment strategies are required to improve patient outcomes. Concerns of toxicity have limited enthusiasm for the utilization of re-irradiation as a treatment option. However, using modern imaging technology and precision radiotherapy delivery techniques re-irradiation has proven a feasible option achieving both a palliative benefit and prolongation of survival with low toxicity rates. The evolution of re-irradiation as a treatment modality for recurrent grade 4 glioma is reviewed. In addition, potential targeted radiosensitizers to be used in conjunction with re-irradiation are also discussed.
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Oral hairy leukoplakia arising in a patient with hairy cell leukaemia: the first reported case
Oral hairy leukoplakia (OHL) is an oral mucosal lesion that is associated with Epstein-Barr virus infection. It commonly presents as an asymptomatic, non-removable white patch on the lateral borders of the tongue in individuals who are immunocompromised. Historically, OHL was thought to be pathognomonic of HIV infection; however, it is now an established phenomenon in a range of conditions affecting immune competence. Hairy cell leukaemia (HCL) is a rare chronic B cell lymphoproliferative disease named after the distinctive cytology of the atypical cells. We report the first case of OHL arising in an individual with HCL that resolved following remission of the haematological malignancy.
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Giant hiatal hernia: beware of the supine ICU chest X-ray!
Description
An 85-year old woman with a medical history of mild hiatal hernia was admitted to the medical intensive care unit for respiratory distress associated with hypoxaemia and hypercapnia. A diagnosis of cardiogenic oedema was suspected. The situation slightly improved after high-dose diuretics and non-invasive ventilation. The anteroposterior supine chest X-ray revealed a right thoracic opacity. The patient was transferred to the pulmonology unit. A classical erected posteroanterior chest X-ray revealed a large air-fluid level in the right hemithorax (figure 1). An hydropneumothorax or a lung abscess was suspected. A chest CT scan revealed a giant hiatal hernia containing the stomach, the first duodenum, the spleen, the caudal part of the pancreas and the left colic flexure, all elevated in the right hemithorax (figure 2A–C; ). A laparoscopic surgical procedure was performed which involved the excision of the hernia sac, a suture repair of...
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Risk Stratification in Cervical Cancer Screening by Complete Screening History– Applying Bioinformatics to a General Screening Population
Abstract
Women screened for cervical cancer in Sweden are currently treated under a one-size-fits-all programme, which has been successful in reducing the incidence of cervical cancer but does not use all of the participants' available medical information. This study aimed to use women's complete cervical screening histories to identify diagnostic patterns that may indicate an increased risk of developing cervical cancer. A nationwide case-control study was performed where cervical cancer screening data from 125,476 women with a maximum follow-up of 10 years were evaluated for patterns of SNOMED diagnoses. The cancer development risk was estimated for a number of different screening history patterns and expressed as Odds Ratios (OR), with a history of 4 benign cervical tests as reference, using logistic regression. The overall performance of the model was moderate (64% accuracy, 71% Area Under Curve (AUC)) with 61-62% of the study population showing no specific patterns associated with risk. However, predictions for high-risk groups as defined by screening history patterns were highly discriminatory with ORs ranging from 8 to 36. The model for computing risk performed consistently across different screening history lengths, and several patterns predicted cancer outcomes. The results show the presence of risk-increasing and risk-decreasing factors in the screening history. Thus it is feasible to identify subgroups based on their complete screening histories. Several high-risk subgroups identified might benefit from an increased screening density. Some low-risk subgroups identified could likely have a moderately reduced screening density without additional risk. This article is protected by copyright. All rights reserved.
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Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer
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HSPA8 as a novel fusion partner of NR4A3 in extraskeletal myxoid chondrosarcoma
Abstract
Extraskeletal myxoid chondrosarcoma (EMC) is a very rare sarcoma most often arising in the soft tissue. Rare EMC of the bone have been reported. EMC exhibits distinctive clinico-pathological and genetic features; however, despite the name, it lacks any feature of cartilaginous differentiation. EMC is characterized by the rearrangement of the NR4A3, which, in most cases (about 62-75%), is fused with EWSR1 and less frequently with other partners, including TAF15 (27%), TCF12 (4%), TFG and FUS. We herein report the identification by whole-transcriptome sequencing of HSPA8 as a novel fusion partner of NR4A3 in a case of EMC. FISH analysis confirmed the presence of a genomic HSPA8-NR4A3 translocation in the vast majority of tumour cells. Our findings expand the spectrum of NR4A3 fusion partners involved in EMC pathobiology. This article is protected by copyright. All rights reserved.
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The evolving role for re-irradiation in the management of recurrent grade 4 glioma
Abstract
Although significant gains have been realized in the management of grade 4 glioma, the majority of these patients will ultimately suffer local recurrence within the prior field of treatment. Clearly, novel local treatment strategies are required to improve patient outcomes. Concerns of toxicity have limited enthusiasm for the utilization of re-irradiation as a treatment option. However, using modern imaging technology and precision radiotherapy delivery techniques re-irradiation has proven a feasible option achieving both a palliative benefit and prolongation of survival with low toxicity rates. The evolution of re-irradiation as a treatment modality for recurrent grade 4 glioma is reviewed. In addition, potential targeted radiosensitizers to be used in conjunction with re-irradiation are also discussed.
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A rare case of a non-traumatic neck of femur fracture in a 17-year-old boy associated with vitamin D deficiency
Hip fractures in the young, healthy population are rare and often the result of high-energy trauma. A previously healthy 17-year-old patient presented to our institution with a 5-week history of left hip and knee pain in the absence of any trauma. Pelvic radiograph revealed a subacute left femoral neck fracture. He subsequently underwent surgical fixation and made an uneventful recovery. Further endocrine evaluation revealed isolated vitamin D deficiency to be the likely underlying cause for this fracture. Multiple previous opportunities were missed to identify the cause for this patient's symptoms. An intracapsular fracture in a young adult requires early recognition and prompt anatomical reduction. This case emphasises the need to maintain a high index of suspicion for atraumatic fractures in healthy adolescents with unexplained joint pain. Further endocrine and metabolic investigations are warranted, and isolated vitamin D deficiency must be considered as a potential causative factor.
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A Bare-Bones Approach
Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 60-year-old woman with type 1…
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Patient perceptions of symptoms and concerns during cancer chemotherapy: ‘affects my family’ is the most important
Abstract
Background
Cancer chemotherapy is associated with a variety of side effects/adverse events. It is very important that patients adhere to the planned chemotherapy regimen, which necessitates a minimum of side effects and that these side effects be kept under control. We have investigated patients' concerns and symptoms during chemotherapy with the aim to seek solutions that will improve patients' quality of life during chemotherapy.
Methods
Forty-nine patients with malignant diseases on parenteral antineoplastic agents were sequentially enrolled in this study. These patients completed a questionnaire consisting of 42 items related to non-physical concerns and 52 items of physical symptoms related to chemotherapy. Each patient was also asked to select the three items among these 94 items which affected him/her the most.
Results
The median age of the cancer patients was 62 years and the male-to-female ratio was 18:31. Among the non-physical concerns, the most frequently chosen concern was 'affects my family or partner,' followed by anxiety related to treatment. Regarding the physical symptoms, the most frequent complaints were fatigue, alopecia and constipation, while the most troublesome symptoms were nausea, poor taste and paresthesia. Overall, the most frequently expressed concerns were 'affects my family or partner' and anxiety related to treatment. Male patients suffered most from fever, fatigue and nausea, and female patients complained more of poor taste and gastrointestinal problems.
Conclusion
Patient perceptions of adverse events associated with cancer chemotherapy apparently have changed from physical symptoms to non-physical concerns. In our patient cohort 'affects my family or partner' was the most important concern. One important point to note is that female patients often complained of poor taste because this meant they were unable to cook well.
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Is hyperbaric oxygen therapy available for all kinds of radiation necrosis?
Source:Cancer/Radiothérapie
Author(s): Y. Benderli Cihan
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