A rounded opacity silhouetting the left heart border and hilum

Pericardial incidentaloma: benign pericardial cyst

από Lin, A. N., Lin, S., Lin, K., Raju, F. στο BMJ Case Reports Last 6 Issues

Μετάφραση άρθρου

Description

A 73-year-old woman with hypertension and atrial fibrillation presented with head and neck injury after mechanical fall. During workup, chest X-ray anteroposterior view (figure 1) revealed a rounded opacity silhouetting the left heart border and hilum. Subsequent contrast-enhanced CT of the chest showed single, 6.4 cm, rounded, well-defined, thin-walled, non-enhanced, low attenuated (–20 and 20 Hounsfield Unit) and homogenous cyst-like structure at the left mediastinum connected to pericardial recesses and not attached to adjacent structures (figure 2A–C). Transthoracic echocardiogram ruled out left ventricular aneurysm, aortic aneurysm, solid tumour and outflow tracts obstruction. Although bronchogenic cyst, oesophageal duplication cyst, thymic tumour and mediastinal lymphoma were considered as possible differentials, radiological features such as CT appearance, homogenous attenuation, unrelated to the underlying structures favoured pericardial cyst. Since patient was asymptomatic, patient and family member were unwilling to undergo surgical removal and pathological confirmation. Follow-up with non-enhanced CT of...

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Transient hemiparaesthesias and dysarthria

Mitral Stenosis

από Oehler, A. C., Sullivan, P. D., Mansoor, A. M. στο BMJ Case Reports Last 6 Issues

Μετάφραση άρθρου

Description

A previously healthy 29-year-old Mexican woman presented to an emergency department with transient hemiparaesthesias and dysarthria. There was no evidence of stroke on cross-sectional imaging of the head, and she was discharged without a clear diagnosis. Two days later, she returned with acute abdominal pain. Abdominal imaging revealed complete occlusion of the right renal artery, prompting emergency embolectomy. Following the procedure, she developed acute haemoptysis, dyspnoea and hypoxaemia. Chest imaging demonstrated evidence of pulmonary venous hypertension. Cardiac auscultation revealed an opening snap followed by a diastolic murmur with presystolic accentuation. These sounds were better appreciated in combination with phonocardiography, a technique supplanted by echocardiography in the 1970s1 that visualised heart sounds (video 1). An echocardiogram confirmed the presence of mitral stenosis (MS), unifying the syndrome of embolic phenomena, haemoptysis and pulmonary hypertension. She underwent successful mitral valve replacement and has since returned to normal...

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Reproductive factors, exogenous hormone use, and risk of pancreatic cancer in postmenopausal women

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Geoffrey C. Kabat, Victor Kamensky, Thomas E. Rohan
IntroductionThe epidemiologic literature on menstrual and reproductive factors associated with pancreatic cancer has yielded weak and inconsistent evidence of an association. Furthermore, few cohort studies have examined the association of exogenous hormone use, including type and duration, with this disease. The aim of this study was to assess the association of these exposures with risk of pancreatic cancer in a large cohort of postmenopausal women.MethodsWe used data from the Women's Health Initiative on 1003 cases of pancreatic cancer diagnosed among 158,298 participants over 14.3 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations of interest.ResultsBeing parous vs. nulliparous was associated with reduced risk (HR=0.84, 95% CI 0.70–1.00), and women who had 1–2 and 3–4 births were at decreased risk compared to nulliparous women, whereas women who had >5 births showed no decrease in risk. Compared to women who gave birth between the ages of 20–29, women who gave birth at age 30 or above were at increased risk (HR 1.23, 95% CI 1.00–1.53, p for trend 0.003). Other reproductive factors and exogenous hormone use were not associated with risk.ConclusionsTogether with the existing literature on this topic, our results suggest that reproductive and hormonal exposures are unlikely to play an important role in the etiology of pancreatic cancer.



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Reproductive factors, exogenous hormone use, and risk of pancreatic cancer in postmenopausal women

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Geoffrey C. Kabat, Victor Kamensky, Thomas E. Rohan
IntroductionThe epidemiologic literature on menstrual and reproductive factors associated with pancreatic cancer has yielded weak and inconsistent evidence of an association. Furthermore, few cohort studies have examined the association of exogenous hormone use, including type and duration, with this disease. The aim of this study was to assess the association of these exposures with risk of pancreatic cancer in a large cohort of postmenopausal women.MethodsWe used data from the Women's Health Initiative on 1003 cases of pancreatic cancer diagnosed among 158,298 participants over 14.3 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations of interest.ResultsBeing parous vs. nulliparous was associated with reduced risk (HR=0.84, 95% CI 0.70–1.00), and women who had 1–2 and 3–4 births were at decreased risk compared to nulliparous women, whereas women who had >5 births showed no decrease in risk. Compared to women who gave birth between the ages of 20–29, women who gave birth at age 30 or above were at increased risk (HR 1.23, 95% CI 1.00–1.53, p for trend 0.003). Other reproductive factors and exogenous hormone use were not associated with risk.ConclusionsTogether with the existing literature on this topic, our results suggest that reproductive and hormonal exposures are unlikely to play an important role in the etiology of pancreatic cancer.



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Mitral Stenosis

Description

A previously healthy 29-year-old Mexican woman presented to an emergency department with transient hemiparaesthesias and dysarthria. There was no evidence of stroke on cross-sectional imaging of the head, and she was discharged without a clear diagnosis. Two days later, she returned with acute abdominal pain. Abdominal imaging revealed complete occlusion of the right renal artery, prompting emergency embolectomy. Following the procedure, she developed acute haemoptysis, dyspnoea and hypoxaemia. Chest imaging demonstrated evidence of pulmonary venous hypertension. Cardiac auscultation revealed an opening snap followed by a diastolic murmur with presystolic accentuation. These sounds were better appreciated in combination with phonocardiography, a technique supplanted by echocardiography in the 1970s1 that visualised heart sounds (video 1). An echocardiogram confirmed the presence of mitral stenosis (MS), unifying the syndrome of embolic phenomena, haemoptysis and pulmonary hypertension. She underwent successful mitral valve replacement and has since returned to normal...

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Uncommon presentation of adult-form scimitar syndrome associated with single left pulmonary vein in a pregnant woman

Scimitar syndrome is the constellation of malformations including an abnormal venous drainage of the right lung into the inferior vena cava, associated with the right lung and systemic supply to the right lung. The anomalous vein looks like the curved, Turkish sword (scimitar), hence the name.

The adult form of scimitar syndrome is rare, and it is usually an incidental diagnosis based on the characteristic finding on radiological imaging since the patients are usually asymptomatic or with minimal symptoms.

Our patient presented with a rare presentation of scimitar syndrome, which is tachyarrhythmia (sinus tachycardia, with episodes of supraventricular tachycardia). The diagnosis of scimitar syndrome was made based on the typical radiological finding of the anomalous venous drainage on CT angiography. Our patient does not have the full spectrum of the scimitar syndrome; therefore, she did not suffer from the usual complication (pulmonary hypertension). She was treated with ablation without surgical intervention.

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Mitral valve vegetation diagnosed with oesophageal ultrasound with bronchoscope (EUS-B)

Oesophageal ultrasound with bronchoscope (EUS-B) is designed to evaluate mediastinal structures. We describe a case of a 78-year-old woman who presented with altered mental status for 2 weeks. CT head revealed a subacute infarct in the right middle cerebral artery distribution. She was also found to have a lung mass on chest imaging. EUS-B-guided fine needle aspiration demonstrated the presence of adenocarcinoma in station 7 lymph node and in the mass. Immunohistochemistry confirmed it to be a lung primary as the Thyroid Transcription Factor-1 (TTF-1) was strongly positive. During the procedure, the cardiac valves were evaluated, and a mitral valve vegetation was noted. Formal echocardiography confirmed the presence of the vegetation. During hospital stay, the patient developed fever. Her blood cultures grew oxacillin-resistant Staphylococcus aureus. She was subsequently treated for infective endocarditis. We suggest that the use of EUS-B to routinely scan adjacent structures during a procedure may help obtain additional clinical information that may be critical to patient management.

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Double hit lymphoma presenting as haemophagocytic lymphohistiocytosis

Description

A 67-year-old woman with history of severe rheumatoid arthritis and use of multiple biologics including infliximab, tocilizumab and abatacept presented with fever of 39.1°C and severe pancytopenia (white blood cell count (WBC)=1.0x10⁹/L,  absolute neutrophil count (ANC)=0.55x10⁹/L, haemoglobin=8.7 g/dL, platelets=46x10⁹/L). As part of the pancytopenia evaluation, imaging (CT of the chest, abdomen and pelvis) showed diffuse lymphadenopathy. Further evaluation revealed an elevated ferritin (8564 ng/mL), hypofibrinogenaemia (fibrinogen=95 mg/dL), elevated triglycerides (399 mg/dL) and a soluble interleukin 2 receptor level of 41 167 units/mL, satisfying diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH). A subsequent bone marrow biopsy also revealed morphological evidence of haemophagocytosis (figure 1A), in addition to a population of very large and atypical mononuclear cells with markedly irregular, folded nuclear contours, prominent nucleoli and moderate amounts of cytoplasm (figure 1B,C). A similar large cell infiltrate was identified in the left axillary lymph node, causing complete effacement of nodal architecture (figure...

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Anaemia and respiratory failure in a child: can it be idiopathic pulmonary haemosiderosis?

We present an 8-year-old male child admitted with cough and high-grade fever for 7 days and respiratory difficulty for 2 days. There was a history of blood transfusion at 2 years of age during a respiratory illness. The child was anaemic, tachycardic, tachypnoeic and hypoxic at presentation. Chest examination revealed equal air entry with fine crackles bilaterally. Blood reports were suggestive of anaemia (haemoglobin 6.5 g/dL), leucocytosis and high C reactive protein levels. Chest radiograph revealed bilateral air space opacities involving diffuse lung fields, right more than left. Relevant microbiological workup was negative. Based on the clinical scenario and investigations, a provisional diagnosis of pulmonary haemosiderosis was kept. The patient was started on intravenous pulse methylprednisolone. Fibre-optic bronchoscopy was done following recovery from the acute event. Bronchoalveolar lavage demonstrated a significant number of haemosiderin-laden macrophages confirming pulmonary haemosiderosis.

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A rare case of thrombotic microangiopathy triggered by acute pancreatitis

Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later.

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Novel use of combination of electromyography and ultrasound to guide quadratus lumborum block after open appendicectomy

The quadratus lumborum (QL) block facilitates the administration of anaesthesia to the anterior abdominal wall. The use of ultrasound (US) improves the accuracy of the QL block and reduces the risk of adverse events. Electromyography (EMG) in combination with US for muscle plane blocks has not been described previously. We postulated that the addition of EMG-guided needle positioning might assist the execution of this block. This case report describes the first use of combined needle EMG and US to carry out a QL block performed for postoperative analgesia following an open appendicectomy.

http://ift.tt/2pQKM16

Pericardial incidentaloma: benign pericardial cyst

Description

A 73-year-old woman with hypertension and atrial fibrillation presented with head and neck injury after mechanical fall. During workup, chest X-ray anteroposterior view (figure 1) revealed a rounded opacity silhouetting the left heart border and hilum. Subsequent contrast-enhanced CT of the chest showed single, 6.4 cm, rounded, well-defined, thin-walled, non-enhanced, low attenuated (–20 and 20 Hounsfield Unit) and homogenous cyst-like structure at the left mediastinum connected to pericardial recesses and not attached to adjacent structures (figure 2A–C). Transthoracic echocardiogram ruled out left ventricular aneurysm, aortic aneurysm, solid tumour and outflow tracts obstruction. Although bronchogenic cyst, oesophageal duplication cyst, thymic tumour and mediastinal lymphoma were considered as possible differentials, radiological features such as CT appearance, homogenous attenuation, unrelated to the underlying structures favoured pericardial cyst. Since patient was asymptomatic, patient and family member were unwilling to undergo surgical removal and pathological confirmation. Follow-up with non-enhanced CT of...

http://ift.tt/2qmmz6w

Neuregulin 1 allosterically enhances the anti-tumor effects of the non-competing anti-HER3 antibody 9F7-F11 by increasing its binding to HER3

Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized that in NRG1-expressing tumors, where the ligand is present before antibody treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor binding have a higher receptor-neutralizing action than antibodies competing with the ligand for binding to HER3. Using time resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a non-ligand competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6, Mab205.10.2 and MOR09825) is decreased. Moreover, 9F7-F11 showed higher efficacy than antibodies that compete with the ligand for binding to HER3. Specifically, 9F7-F11 inhibition of cell proliferation and of HER3/AKT/ERK1/2 phosphorylation as well as 9F7-F11-dependent cell- mediated cytotoxicity were higher in cancer cells pre-incubated with recombinant NRG1 compared with cells directly exposed to the anti-HER3 antibody. This translated in vivo into enhanced growth inhibition of NRG1-expressing BxPC3 pancreatic, A549 lung and HCC-1806 breast cell tumor xenografts in mice treated with 9F7-F11 compared with H4B-121. Conversely, both antibodies had similar anti-tumor effect in NRG1-negative HPAC pancreatic carcinoma cells. In conclusion, the allosteric modulator 9F7-F11 shows increased anti-cancer effectiveness in the presence of NRG1 and thus represents a novel treatment strategy for NRG1-addicted tumors.

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Neuregulin 1 allosterically enhances the anti-tumor effects of the non-competing anti-HER3 antibody 9F7-F11 by increasing its binding to HER3

Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized that in NRG1-expressing tumors, where the ligand is present before antibody treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor binding have a higher receptor-neutralizing action than antibodies competing with the ligand for binding to HER3. Using time resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a non-ligand competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6, Mab205.10.2 and MOR09825) is decreased. Moreover, 9F7-F11 showed higher efficacy than antibodies that compete with the ligand for binding to HER3. Specifically, 9F7-F11 inhibition of cell proliferation and of HER3/AKT/ERK1/2 phosphorylation as well as 9F7-F11-dependent cell- mediated cytotoxicity were higher in cancer cells pre-incubated with recombinant NRG1 compared with cells directly exposed to the anti-HER3 antibody. This translated in vivo into enhanced growth inhibition of NRG1-expressing BxPC3 pancreatic, A549 lung and HCC-1806 breast cell tumor xenografts in mice treated with 9F7-F11 compared with H4B-121. Conversely, both antibodies had similar anti-tumor effect in NRG1-negative HPAC pancreatic carcinoma cells. In conclusion, the allosteric modulator 9F7-F11 shows increased anti-cancer effectiveness in the presence of NRG1 and thus represents a novel treatment strategy for NRG1-addicted tumors.

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The association of low penetrance genetic risk modifiers with colorectal cancer in lynch syndrome patients: a systematic review and meta-analysis

Abstract

Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition syndrome accounting for approximately 1000 cases of colorectal cancer (CRC) in the UK annually. LS is characterised by autosomal dominant inheritance and germline mutations in DNA mismatch repair genes. The penetrance is highly variable and the reasons for this have not been fully elucidated. This study investigates whether low penetrance genetic risk factors may result in phenotype modification in LS patients. To conduct a systematic literature review and meta-analysis to assess the association between low penetrance genetic risk modifiers and CRC in LS patients. A systematic review was conducted of the PubMed and HuGENet databases. Eligibility of studies was determined by pre-defined criteria. Included studies were analysed via the per-allele model and assessed by pooled odds ratios and establishing 95% confidence intervals. Study heterogeneity was assessed via Cochrane's Q statistic and I2 values. Publication bias was evaluated with funnel plots. Subgroup analysis was conducted on gender. Statistical software used was the Metafor package for the R programme version 3.1.3. Sixty-four polymorphisms were identified and sufficient data was available for analysis of ten polymorphisms, with between 279 and 1768 CRC cases per polymorphism. None demonstrated association with CRC risk in LS patients. However in sub-group analysis the polymorphism rs16892766 (8q23.3) was significant in males (OR 1.53, 95% CI 1.12–2.10). The variable phenotype presentation of the disease still remains largely unexplained, and further investigation is warranted. Other factors may also be influencing the high variability of the disease, such as environmental factors, copy number variants and epigenetic alterations. Investigation into these areas is needed as well as larger and more definitive studies of the polymorphisms analysed in this study.

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Nicotinic acid phosphoribosyltransferase regulates cancer cell metabolism, susceptibility to NAMPT inhibitors and DNA repair

In the last decade, substantial efforts have been made to identify NAD+ biosynthesis inhibitors, specifically against nicotinamide phosphoribosyltransferase (NAMPT), as preclinical studies indicate their potential efficacy as cancer drugs. However, the clinical activity of NAMPT inhibitors has proven limited, suggesting that alternative NAD+ production routes exploited by tumors confer resistance. Here we show the gene encoding nicotinic acid phosphoribosyltransferase (NAPRT), a second NAD+ producing enzyme, is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature. Both NAPRT and NAMPT increased intracellular NAD+ levels. NAPRT silencing reduced energy status, protein synthesis, and cell size in ovarian and pancreatic cancer cells. NAPRT silencing sensitized cells to NAMPT inhibitors both in vitro and in vivo; similar results were obtained with the NAPRT inhibitor 2-hydroxynicotinic acid. Reducing NAPRT levels in a BRCA2-deficient cancer cell line exacerbated DNA damage in response to chemotherapeutics. In conclusion, NAPRT-dependent NAD+ biosynthesis contributes to cell metabolism and to the DNA repair process in a subset of tumors. This knowledge could be used to increase the efficacy of NAMPT inhibitors and chemotherapy.

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The Relationship between Symptom Prevalence, Body Image and Quality of Life in Asian Gynecologic Cancer Patients

Abstract

Objective

Gynecologic cancer is associated with long-term effects that can be both physical and emotional. We examined symptom prevalence and body image disturbance in patients with gynecologic cancer, and their association with quality of life. Predictors of clinically-relevant body image disturbance were examined.

Methods

A sample of patients in Singapore (n = 104) was assessed for symptom prevalence, quality of life, and body image dissatisfaction. Clinical factors were extracted from medical records.

Results

The most frequently reported symptoms were fatigue, bloatedness, weight gain, constipation, hot flashes, and pelvic pain. Approximately one quarter patients reported feeling less physically attractive and dissatisfied with their body. Ordinary least squares regression indicated that symptom prevalence alone predicted physical well-being, b = 1.17, p <. 001, 95% CI [-1.58,-0.76] and functional well-being, b = 0.94, p <. 001, 95% CI [-1.41,-0.48]. Body image dissatisfaction significantly predicted emotional well-being, b = 0.22, p =. 01, 95% CI [-0.38,-0.07]. Younger age was a significant risk factor for clinically-relevant score of body image distress, OR = 0.95 per year older, 95% CI [0.92, 0.99], p = .02.

Conclusions

Symptom prevalence and body image dissatisfaction were associated with different domains of quality of life. Emotional well-being was better explained by the perceived state of the body, rather than the extent of symptoms. Patients who are younger appear particularly susceptible to body image disturbance.

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Structural Behavior of the Endothelial Glycocalyx Is Associated With Pathophysiologic Status in Septic Mice: An Integrated Approach to Analyzing the Behavior and Function of the Glycocalyx Using Both Electron and Fluorescence Intravital Microscopy.

BACKGROUND: The endothelial surface layer (ESL) regulates vascular permeability to maintain fluid homeostasis. The glycocalyx (GCX), which has a complex and fragile ultrastructure, is an important component of the ESL. Abnormalities of the GCX have been hypothesized to trigger pathological hyperpermeability. Here, we report an integrated in vivo analysis of the morphological and functional properties of the GCX in a vital organ. METHODS: We examined the behavior of the ESL and GCX, using both electron microscopy (EM) and intravital microscopy (IVM). We also compared morphological changes in the ESL of mouse skin in a glycosidase-treated and control group. Combined approaches were also used to examine both morphology and function in a lipopolysaccharide-induced septic model and the pathophysiological features of leukocyte-endothelial interactions and in vivo vascular permeability. RESULTS: Using IVM, we identified an illuminated part of the ESL as the GCX and confirmed our observation using morphological and biochemical means. In septic mice, we found that the GCX was thinner than in nonseptic controls in both an EM image analysis (0.98 +/- 2.08 nm vs 70.68 +/- 36.36 nm, P

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A Structured Transfer of Care Process Reduces Perioperative Complications in Cardiac Surgery Patients.

INTRODUCTION: Serious complications are common during the intensive care of postoperative cardiac surgery patients. Some of these complications may be influenced by communication during the process of handover of care from the operating room to the intensive care unit (ICU) team. A structured transfer of care process may reduce the rate of communication errors and perioperative complications. METHODS: We hypothesized that a collaborative, comprehensive, structured handover of care from the intraoperative team to the ICU team would reduce a specific set of postoperative complications. We tested this hypothesis by developing and introducing a comprehensive multidisciplinary transfer of care process. We measured patient outcomes before and after the intervention using a linkage between 2 care databases: an Anesthesia Information Management System and a critical care complication registry database. RESULTS: There were 1127 total postoperative cardiac surgery admissions during the study period, 550 before and 577 after the intervention. There was no statistical difference between overall complications before and after the intervention (P = .154). However, there was a statistically significant reduction in preventable complications after the intervention (P = .023). DISCUSSION: The main finding of this investigation is that the introduction of a collaborative, comprehensive transfer of care process from the operating room to the ICU was associated with patients suffering fewer preventable complications. (C) 2017 International Anesthesia Research Society

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Tablet e-Logbooks: Four Thousand Clinical Cases and Complications e-Logged by 14 Nondoctor Anesthesia Providers in Nepal.

BACKGROUND: To meet the need for essential surgery across rural Nepal, anesthesia at district level is delivered by nondoctor anesthetists. They require support to maintain confidence and competence, and upgraded professional registration to secure their status. To meet these needs, a distance-blended learning course was pioneered and delivered. A core course requirement was to log all clinical cases; these were logged on a new e-logbook. METHODS: Fourteen nondoctor anesthesia providers working in 12 different districts across Nepal were enrolled in the 1-year course. The course is based on self-completion on a tablet loaded with new learning modules, a resource library, and a case logbook. Continuous educational mentoring was provided by anesthesiologists by phone and email. The logbook included preanesthesia assessment and interventions, American Society of Anesthesiologists (ASA) grading, types of cases and anesthesia given, monitors used, complications, outcomes and free text remarks. Cases were uploaded monthly to a database, and mentors reviewed all logbook entries. RESULTS: The 14 nondoctor anesthesia providers were widely distributed across the country in district, zonal, community, and mission hospitals, and had different levels of clinical experience and caseloads. Logbooks and uploads were regularly completed without difficulty; 1% cases were entered incompletely with no case details provided. A total of 4143 cases were recorded. Annual caseload per nondoctor anesthesia provider ranged from 50 to 788, the majority of which were under spinal anesthesia; 34% of the total cases were cesarean deliveries, of which 99% received spinal anesthesia. Fifty gastrointestinal laparotomies (1% total) were recorded. Ninety-one percent of cases were ASA I, 0.8% ASA III/IV. Pulse oximetry was used in 98% of cases. Complications were recorded in 6% of cases; the most common were circulation problems (69%) including hypotension and occasional bradycardia after spinal anesthesia. Airway complications were usually under ketamine anesthesia requiring basic airway maneuvers; 4 difficult intubations were recorded under general anesthesia. Anesthesia outcomes were good with overall mortality of 0.1% (total 4 cases). Causes of death included severe preeclampsia, sepsis postlaparotomy, and patients with multiorgan failure for minor procedure. CONCLUSIONS: The tablet-based electronic anesthesia logbook was successfully used to record cases, complications, and outcomes across rural Nepal. The nondoctor anesthesia providers had trust and confidence in recording outcomes. It remains to be tested whether an e-logbook would be routinely completed outside of a specific training course. Such a logbook could be incorporated into all continuous professional development programs for rural nondoctor anesthetists. (C) 2017 International Anesthesia Research Society

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Trends in Perioperative Practice and Resource Utilization in Patients With Obstructive Sleep Apnea Undergoing Joint Arthroplasty.

BACKGROUND: Emerging evidence associating obstructive sleep apnea (OSA) with adverse perioperative outcomes has recently heightened the level of awareness among perioperative physicians. In particular, estimates projecting the high prevalence of this condition in the surgical population highlight the necessity of the development and adherence to "best clinical practices." In this context, a number of expert panels have generated recommendations in an effort to provide guidance for perioperative decision-making. However, given the paucity of insights into the status of the implementation of recommended practices on a national level, we sought to investigate current utilization, trends, and the penetration of OSA care-related interventions in the perioperative management of patients undergoing lower joint arthroplasties. METHODS: In this population-based analysis, we identified 1,107,438 (Premier Perspective database; 2006-2013) cases of total hip and knee arthroplasties and investigated utilization and temporal trends in the perioperative use of regional anesthetic techniques, blood oxygen saturation monitoring (oximetry), supplemental oxygen administration, positive airway pressure therapy, advanced monitoring environments, and opioid prescription among patients with and without OSA. RESULTS: The utilization of regional anesthetic techniques did not differ by OSA status and overall 50% and a concurrent decrease in opioid prescription. Interestingly, while the absolute number of patients with OSA receiving perioperative oximetry, supplemental oxygen, and positive airway pressure therapy significantly increased over time, the proportional use significantly decreased by approximately 28%, 36%, and 14%, respectively. A shift from utilization of intensive care to telemetry and stepdown units was seen. CONCLUSIONS: On a population-based level, the implementation of OSA-targeted interventions seems to be limited with some of the current trends virtually in contrast to practice guidelines. Reasons for these findings need to be further elucidated, but observations of a dramatic increase in absolute utilization with a proportional decrease may suggest possible resource constraints as a contributor. (C) 2017 International Anesthesia Research Society

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Red Blood Cell Transfusion and Surgical Site Infection After Colon Resection Surgery: A Cohort Study.

BACKGROUND: Surgical site infections (SSIs) after colon surgery remain a critical safety issue. Patients with an SSI have an increased risk of death, prolonged hospitalization, and increased costs of care. Red blood cell (RBC) transfusion is given during the perioperative period to increase blood oxygen delivery, but it is associated with complications, including infection. We hypothesized that RBC transfusion would be associated with increased SSI risk in patients undergoing colon resection surgery. METHODS: A retrospective cohort study was performed using the 2014 National Surgical Quality Improvement Program participant use file. Patients who had colon resection surgery were identified using current procedural terminology codes. The association between perioperative RBC transfusion and superficial and deep incisional SSIs, organ space SSIs, and postoperative septic shock was modeled using logistic regression with propensity score analysis. RESULTS: Of 23,388 patients who had colon resection surgery, 1845 (7.9%) received perioperative RBC transfusion. After controlling for confounders with propensity score analysis and inverse probability of treatment weighting, RBC transfusion had no apparent association with superficial incisional SSI (odds ratio [OR], 1.18; 99% confidence interval [CI], 0.48-2.88) or deep incisional SSI (OR, 1.47; 99% CI, 0.23-9.43). However, RBC transfusion appeared to be associated with increased risk of organ space SSI (OR, 2.93; 99% CI, 1.43-6.01) and septic shock (OR, 9.23; 99% CI, 3.53-24.09). CONCLUSIONS: RBC transfusion has no apparent association with increased risk for incisional SSIs, but may be associated with increased risk for organ space SSI and septic shock after colon resection surgery. (C) 2017 International Anesthesia Research Society

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Preoperative Low-Dose Aspirin Exposure and Outcomes After Emergency Neurosurgery for Traumatic Intracranial Hemorrhage in Elderly Patients.

BACKGROUND: Antiplatelet medications are usually discontinued before elective neurosurgery, but this is not an option for emergent neurosurgery. We performed a retrospective cohort study to examine whether preoperative aspirin use was associated with worse outcomes after emergency neurosurgery in elderly patients. METHODS: We analyzed all cases of emergency neurosurgical procedures for traumatic intracranial hemorrhage from 2008 to 2012 at a level 1 trauma center. Demographics, comorbidities, and outcomes were compared for patients >=65 years by preoperative aspirin exposure. Exclusion criteria were: (1) polytrauma, (2) concomitant use of other preoperative anticoagulants or antiplatelet agents, (3) surgical indication other than subdural, extradural, or intraparenchymal hemorrhage, and (4) repeat neurosurgical procedures within a single admission. Estimated intraoperative blood loss, postprocedural intracranial bleeding requiring reoperation, death in hospital, intensive care unit, and hospital lengths of stay and perioperative blood product transfusion from 48 hours before 48 hours after surgery were the study outcomes. We also examined whether platelet transfusion had an impact on outcomes for patients on aspirin. RESULTS: The cohort included 171 patients. Patients receiving preoperative aspirin (n = 87, 95% taking 81 mg/day) were the same age as patients not receiving aspirin (n = 84; 78.3 +/- 7.8 vs 75.9 +/- 7.9 years, P > .05), had slightly higher admission Glasgow Coma Scale scores (12.8 +/- 3.4 vs 11.4 +/- 4, P = .02) and tended to have more coronary artery disease (P =65 years undergoing emergency neurosurgery for traumatic intracranial hemorrhage, preoperative low-dose aspirin treatment was not associated with increased perioperative bleeding, hospital lengths of stay, or in-hospital mortality. (C) 2017 International Anesthesia Research Society

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Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.

BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is often -collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is -re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period. METHODS: We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2-+NO3-, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2-+NO3-) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008; and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2-+NO3- and H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P

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Stroke Volume Variation and Pulse Pressure Variation Are Not Useful for Predicting Fluid Responsiveness in Thoracic Surgery.

BACKGROUND: Stroke volume variation (SVV) and pulse pressure variation (PPV) are used as indicators of fluid responsiveness, but little is known about the usefulness of these dynamic preload indicators in thoracic surgery, which involves an open thoracic cavity and one-lung ventilation (OLV). Therefore, we investigated whether SVV and PPV could predict fluid responsiveness, and whether the thresholds of these parameters should be adjusted for thoracic surgery. METHODS: This was a prospective, controlled study conducted in a tertiary care center. Eighty patients scheduled for an elective lobectomy requiring OLV were included (n = 40, video-assisted thoracoscopic surgery (VATS); n = 40, open thoracotomy). Twenty minutes after opening the thoracic cavity, 7 mL/kg hydroxyethyl starch was administered for 30 minutes. Various hemodynamic parameters were measured before and after fluid challenge. RESULTS: Among the 80 patients enrolled in this study, 37% were fluid responders (increase in stroke volume index >=10%). SVV before fluid challenge was not different between nonresponders and responders (mean +/- SD: 7.1 +/- 2.7% vs 7.4 +/- 2.6%, P = .68). This finding was true regardless of whether the surgery involved open thoracotomy or VATS. PPV before fluid challenge showed the difference between nonresponders and responders (mean +/- SD: 6.9 +/- 3.0% vs 8.4 +/- 3.2%; P = .045); however, the sensitivity and specificity of the threshold value (PPV = 7%) were low (58% and 62%, respectively) and the area under the receiver operating characteristics curve was only 0.63 (95% confidence interval, 0.52-0.74; P = .041). CONCLUSIONS: Dynamic preload indicators are not useful for predicting fluid responsiveness in VATS or open thoracic surgery. (C) 2017 International Anesthesia Research Society

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The Labor Analgesia Requirements in Nulliparous Women Randomized to Epidural Catheter Placement in a High or Low Intervertebral Space.

BACKGROUND: We hypothesized that an epidural catheter placed in a lower vertebral interspace will require less medication for labor analgesia. METHODS: Nulliparous women requesting neuraxial labor analgesia were randomized to epidural catheter placement at the ultrasound-confirmed L1-2 or L4-5 interspace. Patient-controlled epidural analgesia and breakthrough manual epidural boluses of 10 mL of 0.125% bupivacaine with 50 [micro]g of fentanyl or 8 mL of 2% lidocaine were utilized. Abdominal and perineal pain scores were assessed at 30 and 60 minutes after standardized initiation of epidural analgesia. Pain scores during pushing were assessed after delivery. The primary outcome was the proportion of patients requiring manual boluses and was compared using a [chi]2 test. Secondarily, we analyzed the number of boluses given in early (up to 4 hours before delivery) versus late labor using [chi]2 tests and the pain scores using Mann-Whitney U tests, with adjustment of P values for multiple testing. RESULTS: We analyzed 148 patients. Overall, the percentage of patients in the low versus high groups who required manual boluses was 46% vs 51% (P = 1.0). For the 56 patients in each group who delivered vaginally, 22 (52%) vs 20 (48%) manual boluses were given to the low epidural group in early versus late labor, compared to 9 (20%) vs 36 (80%) in the high epidural group (P = .014). There was no statistical difference in patient-controlled epidural analgesia requirements or patient satisfaction. Comparing the low versus high groups, the median (interquartile range) pain scores were: 3 (1, 6) vs 0 (0, 2) (P = .013) at 30 minutes and 1 (1, 3) vs 0 (0, 1) (P = .013) at 60 minutes for abdominal pain; 0 (0, 2) vs 1 (1, 3) (P = .36) and 0 (0, 1) vs 1 (1, 3) (P = .014) at these same time points for perineal pain; and 1 (0, 5) vs 0 (0, 3) (P = .9) for abdominal and 2 (0, 5) vs 4 (1, 8) (P = .025) for perineal pain during pushing. The percentage of patients who underwent instrumental delivery was 15% vs 5% (P = .06) for the low versus high group. CONCLUSIONS: An L4-5 epidural catheter initially provides less relief of abdominal pain but more relief of perineal labor pain. Patients with an L4-5 catheter require more manual boluses during early labor but less during late labor. The possible association of low epidural catheters with instrumental delivery merits further investigation. (C) 2017 International Anesthesia Research Society

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Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.

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Molecular signaling in multiple myeloma: association of RAS/RAF mutations and MEK/ERK pathway activation

Molecular signaling in multiple myeloma: association of RAS/RAF mutations and MEK/ERK pathway activation

Oncogenesis 6, e337 (May 2017). doi:10.1038/oncsis.2017.36

Authors: J Xu, N Pfarr, V Endris, E K Mai, N H Md Hanafiah, N Lehners, R Penzel, W Weichert, A D Ho, P Schirmacher, H Goldschmidt, M Andrulis & M S Raab

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The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen signalling in prostate cancer cells

The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen signalling in prostate cancer cells

Oncogenesis 6, e333 (May 2017). doi:10.1038/oncsis.2017.32

Authors: S Koushyar, G Economides, S Zaat, W Jiang, C L Bevan & D A Dart

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Cyclin-dependent kinase 7 is a therapeutic target in high-grade glioma

Cyclin-dependent kinase 7 is a therapeutic target in high-grade glioma

Oncogenesis 6, e336 (May 2017). doi:10.1038/oncsis.2017.33

Authors: S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day & T G Johns

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Mint3-mediated L1CAM expression in fibroblasts promotes cancer cell proliferation via integrin α5β1 and tumour growth

Mint3-mediated L1CAM expression in fibroblasts promotes cancer cell proliferation via integrin α5β1 and tumour growth

Oncogenesis 6, e334 (May 2017). doi:10.1038/oncsis.2017.27

Authors: H J Nakaoka, Z Tanei, T Hara, J S Weng, A Kanamori, T Hayashi, H Sato, A Orimo, K Otsuji, K Tada, T Morikawa, T Sasaki, M Fukayama, M Seiki, Y Murakami & T Sakamoto

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MicroRNA-645 is an oncogenic regulator in colon cancer

MicroRNA-645 is an oncogenic regulator in colon cancer

Oncogenesis 6, e335 (May 2017). doi:10.1038/oncsis.2017.37

Authors: S T Guo, X Y Guo, J Wang, C Y Wang, R H Yang, F H Wang, X Y Li, H Hondermarck, R F Thorne, Y F Wang, L Jin, X D Zhang & C C Jiang

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Epigenetic pathway inhibitors represent potential drugs for treating pancreatic and bronchial neuroendocrine tumors

Epigenetic pathway inhibitors represent potential drugs for treating pancreatic and bronchial neuroendocrine tumors

Oncogenesis 6, e332 (May 2017). doi:10.1038/oncsis.2017.30

Authors: K E Lines, M Stevenson, P Filippakopoulos, S Müller, H E Lockstone, B Wright, S Grozinsky-Glasberg, A B Grossman, S Knapp, D Buck, C Bountra & R V Thakker

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CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in ovarian cancer patients

CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in ovarian cancer patients

Oncogenesis 6, e331 (May 2017). doi:10.1038/oncsis.2017.29

Authors: C Windmüller, D Zech, S Avril, M Boxberg, T Dawidek, B Schmalfeldt, M Schmitt, M Kiechle & H Bronger

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The influence of a composite hospital volume on outcomes for gastric cancer surgery: A Dutch population-based study

Background

Volume-outcome associations for complex surgical procedures have motivated centralization of care worldwide. The aim of this study was to investigate the association between overall hospital experience with complex upper gastrointestinal (GI) cancer resections and outcomes after gastric cancer surgery.

Methods

Data on all patients (n = 4837) who underwent a resection for non metastatic invasive gastric cancer between 2005 and 2014 were obtained from the Netherlands Cancer Registry (NCR). Annual hospital volume categories were based on the combined volume of gastrectomies, esophagectomies, and pancreatectomies (composite hospital volume). Volume-outcome analyses were performed for lymph node yield, 30-day mortality, and overall survival.

Results

The proportion of gastric cancer resections performed in hospitals with an annual composite hospital volume of ≥40 upper GI cancer resections increased from 6% in 2005 to 80% in 2014. A higher composite hospital volume was univariably associated with a higher lymph node yield, lower 30-day mortality, and increased overall survival. Statistical significance was lost after adjusting for case mix. But, sub group analysis including only elderly patients (≥75 years) showed a significant association between composite hospital volume and 30-day mortality.

Conclusion

In the Netherlands, an increasing proportion of gastric cancer resections is performed in hospitals with a high composite hospital volume of gastric, esophageal, and pancreatic cancer resections. Special attention is warranted to referral of elderly patients, as these patients might specifically benefit from this centralization.

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The influence of a composite hospital volume on outcomes for gastric cancer surgery: A Dutch population-based study

Background

Volume-outcome associations for complex surgical procedures have motivated centralization of care worldwide. The aim of this study was to investigate the association between overall hospital experience with complex upper gastrointestinal (GI) cancer resections and outcomes after gastric cancer surgery.

Methods

Data on all patients (n = 4837) who underwent a resection for non metastatic invasive gastric cancer between 2005 and 2014 were obtained from the Netherlands Cancer Registry (NCR). Annual hospital volume categories were based on the combined volume of gastrectomies, esophagectomies, and pancreatectomies (composite hospital volume). Volume-outcome analyses were performed for lymph node yield, 30-day mortality, and overall survival.

Results

The proportion of gastric cancer resections performed in hospitals with an annual composite hospital volume of ≥40 upper GI cancer resections increased from 6% in 2005 to 80% in 2014. A higher composite hospital volume was univariably associated with a higher lymph node yield, lower 30-day mortality, and increased overall survival. Statistical significance was lost after adjusting for case mix. But, sub group analysis including only elderly patients (≥75 years) showed a significant association between composite hospital volume and 30-day mortality.

Conclusion

In the Netherlands, an increasing proportion of gastric cancer resections is performed in hospitals with a high composite hospital volume of gastric, esophageal, and pancreatic cancer resections. Special attention is warranted to referral of elderly patients, as these patients might specifically benefit from this centralization.

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Obesity and Weight Control: Is There Light at the End of the Tunnel?

Abstract

Purpose of Review

Our global population recently arrived at the landmark figure of seven billion, and the nutrition problems we face are increasing as rapidly, with the longstanding crisis of undernutrition joined by the escalating problem of overconsumption and obesity. Over the past 30 years, it has become clear that control of body weight is as simple as matching energy intake to expenditure, yet how to achieve this in the current obesigenic environment is far from simple. A review of causative mechanisms shows controlling eating behaviour and food intake as central to regulation of body weight, but in an environment where the need to suppress intake is uppermost, there are few physiological mechanisms with which to tackle this.

Recent Findings

Macronutrient composition, energy density, food format (beverages), palatability, portion size and hedonics all influence intake and readily promote overeating. Currently, the most successful obesity treatment is restrictive bariatric surgery, both invasive and expensive, achieving better outcomes than diet and exercise. Despite considerable advances, there remains a critical gap in translation of underpinning knowledge into successful public health outcomes, as recently outlined in the 2nd Lancet series in obesity with no country reporting decreased obesity prevalence in the last 30 years.

Summary

Future contribution may come from better understanding of mechanisms including gut-brain axis and regulation of appetite, the gut microbiome and the genetic underpinning of bodyweight control. Clearly, prevention is the key, with nutrition education required to lead changes in behaviour, and possibly the only viable long-term approach. Whether the global obesity trend can be reversed without significant change in national food policies and/or the built environment however is under debate, and without doubt a major public health challenge for tomorrow if there is to be light at the end of the obesity tunnel.

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Obesity and Weight Control: Is There Light at the End of the Tunnel?

Abstract

Purpose of Review

Our global population recently arrived at the landmark figure of seven billion, and the nutrition problems we face are increasing as rapidly, with the longstanding crisis of undernutrition joined by the escalating problem of overconsumption and obesity. Over the past 30 years, it has become clear that control of body weight is as simple as matching energy intake to expenditure, yet how to achieve this in the current obesigenic environment is far from simple. A review of causative mechanisms shows controlling eating behaviour and food intake as central to regulation of body weight, but in an environment where the need to suppress intake is uppermost, there are few physiological mechanisms with which to tackle this.

Recent Findings

Macronutrient composition, energy density, food format (beverages), palatability, portion size and hedonics all influence intake and readily promote overeating. Currently, the most successful obesity treatment is restrictive bariatric surgery, both invasive and expensive, achieving better outcomes than diet and exercise. Despite considerable advances, there remains a critical gap in translation of underpinning knowledge into successful public health outcomes, as recently outlined in the 2nd Lancet series in obesity with no country reporting decreased obesity prevalence in the last 30 years.

Summary

Future contribution may come from better understanding of mechanisms including gut-brain axis and regulation of appetite, the gut microbiome and the genetic underpinning of bodyweight control. Clearly, prevention is the key, with nutrition education required to lead changes in behaviour, and possibly the only viable long-term approach. Whether the global obesity trend can be reversed without significant change in national food policies and/or the built environment however is under debate, and without doubt a major public health challenge for tomorrow if there is to be light at the end of the obesity tunnel.

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The combined association of alcohol consumption with dementia risk is likely biased due to lacking account of death cases

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A large French multicenter retrospective series of T1-T2N0 vocal cords carcinomas treated with exclusive irradiation

Publication date: Available online 15 May 2017
Source:Cancer/Radiothérapie
Author(s): A. Robert, Y. Pointreau, G. Janoray, É. Bardet, M. Fesneau, P. Garaud, S. Chapet, C. Lafond, O. Dupuis, G. Calais
PurposeThe main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords.Patients and methodsWe retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification.ResultsThe median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4–83.5), 5 years local control was 86.8% (95% CI: 82.3–91.3), specific survival rate was 95% (95% CI: 92.2–97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2–92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy.ConclusionRadiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level.



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A large French multicenter retrospective series of T1-T2N0 vocal cords carcinomas treated with exclusive irradiation

Publication date: Available online 15 May 2017
Source:Cancer/Radiothérapie
Author(s): A. Robert, Y. Pointreau, G. Janoray, É. Bardet, M. Fesneau, P. Garaud, S. Chapet, C. Lafond, O. Dupuis, G. Calais
PurposeThe main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords.Patients and methodsWe retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification.ResultsThe median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4–83.5), 5 years local control was 86.8% (95% CI: 82.3–91.3), specific survival rate was 95% (95% CI: 92.2–97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2–92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy.ConclusionRadiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level.



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Will it be cheese, bologna, or peanut butter?

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The combined association of alcohol consumption with dementia risk is likely biased due to lacking account of death cases

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The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer

Abstract

Ovarian cancer (OC) is one of the three types of malignant tumors in the female reproductive system, and epithelial ovarian cancer (EOC) is its most typical form. Due to the asymptomatic nature of the early stages and resistance to chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current treatments for OC are very limited, and the 5-years survival rate is approximately 30%. Exosomes, which are microvesicles ranging from approximately 30–100 nm in size that are secreted by living cells, can be produced from different cell types and detected in various body fluids. Cancer cells can secrete more exosomes than healthy cells, and more importantly, the content of cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells are considered to be involved in tumor progression and metastasis. As such, exosomes are expected to be potential tools for tumor diagnosis and treatment. In this review, we briefly present the emerging roles of exosomes in OC and summarize related articles about their roles as diagnostic or prognostic biomarkers and in the treatment and drug resistance of OC.

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Will it be cheese, bologna, or peanut butter?

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The combined association of alcohol consumption with dementia risk is likely biased due to lacking account of death cases

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The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer

Abstract

Ovarian cancer (OC) is one of the three types of malignant tumors in the female reproductive system, and epithelial ovarian cancer (EOC) is its most typical form. Due to the asymptomatic nature of the early stages and resistance to chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current treatments for OC are very limited, and the 5-years survival rate is approximately 30%. Exosomes, which are microvesicles ranging from approximately 30–100 nm in size that are secreted by living cells, can be produced from different cell types and detected in various body fluids. Cancer cells can secrete more exosomes than healthy cells, and more importantly, the content of cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells are considered to be involved in tumor progression and metastasis. As such, exosomes are expected to be potential tools for tumor diagnosis and treatment. In this review, we briefly present the emerging roles of exosomes in OC and summarize related articles about their roles as diagnostic or prognostic biomarkers and in the treatment and drug resistance of OC.

http://ift.tt/2qKcJNf

Long-term outcomes of 307 patients after complete thymoma resection

Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and r...

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Long-term outcomes of 307 patients after complete thymoma resection

Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and r...

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Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases

Abstract

Purpose

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point.

Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV_50%). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP.

Results

A total of 47 index lesions and a range of 2–122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6–8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV_50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%.

Conclusions

Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

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MiR-424 functions as a tumor suppressor in glioma cells and is down-regulated by DNA methylation

Abstract

Glioma is one of the most lethal malignancies, and increasing reports revealed that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role in the development and pathology of human gliomas. MiR-424 has been found to be dysregulated in many different types of human cancers. However, the clinical significance and function of miR-424 in glioma remains unclear. Here, based on RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was significantly decreased in glioma tumor tissues than in adjacent non-neoplastic brain tissues, and decreased miR-424 expression was associated with glioma KPS (P = 0.009) and high grades (P = 0.029). In vitro cellular function assays further revealed that miR-424 inhibited cell invasion and migration, and promoted cell apoptosis. In addition, based on DNA methylation analysis on clinical specimens and cell lines, we found miR-424 promoter CpG island was frequently methylated and correlated with glioma high grades (P = 0.035) and IDH mutation status (P = 0.042). Moreover, the promoter CpG island was demethylated by 5-aza-2′-deoxycytidine treatment in a time-dependent manner and the expression levels of miR-424 were gradually induced and increased. Taken together, our data suggest that the promoter region CpG island methylation is associated with tumor suppressive miR-424 silencing and the pathology of human gliomas.

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Assessment of molecular markers demonstrates concordance between samples acquired via stereotactic biopsy and open craniotomy in both anaplastic astrocytomas and glioblastomas

Abstract

The classification, treatment and prognosis of high-grade gliomas has been shown to correlate with the expression of molecular markers (e.g. MGMT promotor methylation and IDH1 mutations). Acquisition of tumor samples may be obtained via stereotactic biopsy or open craniotomy. Between the years 2009 and 2013, 22 patients initially diagnosed with HGGs via stereotactic biopsy, that ultimately underwent open craniotomy for resection of their tumor were prospectively included in an institutional glioma database. MGMT promotor analysis was performed using methylation-specific (MS)-PCR and IDH1R132H mutation analysis was performed using immunohistochemistry. Three patients (13.7%) exhibited IDH1R132H mutations in samples obtained via stereotactic biopsy. Tissue derived from stereotaxic biopsy was demonstrated to have MGMT promotor methylation in ten patients (45.5%), while a non-methylated MGMT promotor was demonstrated in ten patients (45.5%); inconclusive results were obtained for the remaining two patients (9%) within our cohort. The initial histologic grading, IDH1R132H mutation and MGMT promotor methylation results were confirmed using samples obtained during open craniotomy in all but one patient; here inconclusive MGMT promotor analysis was obtained in contrast to that which was obtained via stereotactic biopsy. Tumor samples acquired via stereotactic biopsy provide accurate information with regard to clinically relevant molecular markers that have been shown to impact patient care decisions. The profile of markers analyzed in our cohort was nearly concordant between those samples obtained via stereotactic biopsy or open craniotomy thereby suggesting that clinical decisions may be based on the molecular profile of the tumor samples obtained via stereotactic biopsy.

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Long-term outcomes of 307 patients after complete thymoma resection

Abstract

Background

Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection.

Methods

We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses.

Results

During follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resection had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017).

Conclusions

Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

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Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

Abstract

Background

Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.

Methods

Levels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis.

Results

TCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival.

Conclusions

These findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.

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Recent advances in targeting DNA repair pathways for the treatment of ovarian cancer and their clinical relevance

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency.

http://ift.tt/2pD5N48

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases

Abstract

Purpose

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point.

Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV_50%). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP.

Results

A total of 47 index lesions and a range of 2–122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6–8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV_50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%.

Conclusions

Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

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Long-term outcomes of 307 patients after complete thymoma resection

Abstract

Background

Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection.

Methods

We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses.

Results

During follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resection had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017).

Conclusions

Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

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Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

Abstract

Background

Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.

Methods

Levels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis.

Results

TCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival.

Conclusions

These findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.

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Recent advances in targeting DNA repair pathways for the treatment of ovarian cancer and their clinical relevance

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency.

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Multicenter, Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate 0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues in Normal-Tension Glaucoma

Abstract

Introduction

This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction.

Methods

In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit.

Results

A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (−1.05 ± 1.81 mmHg) and timolol (−1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [−0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively.

Conclusion

This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate.

Funding

Senju Pharmaceutical Co., Ltd.

Trial registration

UMIN Clinical Trials Registry identifier, UMIN000014810.

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Duration of Antiviral Prophylaxis and Risk of Herpes Zoster among Patients Receiving Autologous Hematopoietic Stem Cell Transplants: A Retrospective, Observational Study

Abstract

Introduction

There are no real-world data on antiviral prophylaxis (AP) duration and risk of herpes zoster (HZ) given AP duration in patients receiving autologous hematopoietic stem cell transplants (auto-HSCT). The objectives of this study are to describe the duration of AP and to compare incidence of HZ by AP duration in auto-HSCT patients.

Methods

This is a retrospective, observational database (Marketscan^®) study. This study included patients ≥18 years old who had auto-HSCT during 2009–2013, had chemotherapy within 60 days prior to auto-HSCT (latest chemotherapy date within the 60 days was the study enrollment date), and had continuous health plan enrollment for at least 365 days before and after the study enrollment date. AP duration was the sum of days supply of all AP prescriptions from 30 days before to 365 days after the study enrollment date. Patients were followed from the study enrollment date to the end of continuous health plan enrollment, death, or December 31, 2014 to assess HZ incidence. The Cox proportional hazards model was used to examine the association between the risk of HZ and AP duration.

Results

This study identified 1959 eligible auto-HSCT patients, of whom 93.0% were prescribed AP. Average AP duration was 220 days (SD = 122), while 200 (11%) patients had AP for ≥1 year. HZ incidence was 42.4/1000 person-years (PY) (95% CI 36.5, 49.0) for the overall auto-HSCT cohort. Among patients who received AP, duration of AP prescriptions and HZ incidence were inversely related. Compared with patients who were on AP for 1–89 days, patients with AP duration of 180–269 days [hazard ratio (HR) = 0.576, p = 0.019], 270–359 days (HR = 0.594, p = 0.023), and ≥360 days (HR = 0.309, p < 0.001) had significantly lower risk of HZ.

Conclusion

Auto-HSCT patients are at increased risk for HZ, even when prescribed AP. A safe and effective vaccine against HZ for auto-HSCT patients could be a useful adjunctive prevention strategy.

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Multicenter, Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate 0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues in Normal-Tension Glaucoma

Abstract

Introduction

This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction.

Methods

In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit.

Results

A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (−1.05 ± 1.81 mmHg) and timolol (−1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [−0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively.

Conclusion

This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate.

Funding

Senju Pharmaceutical Co., Ltd.

Trial registration

UMIN Clinical Trials Registry identifier, UMIN000014810.

http://ift.tt/2riikX5

Duration of Antiviral Prophylaxis and Risk of Herpes Zoster among Patients Receiving Autologous Hematopoietic Stem Cell Transplants: A Retrospective, Observational Study

Abstract

Introduction

There are no real-world data on antiviral prophylaxis (AP) duration and risk of herpes zoster (HZ) given AP duration in patients receiving autologous hematopoietic stem cell transplants (auto-HSCT). The objectives of this study are to describe the duration of AP and to compare incidence of HZ by AP duration in auto-HSCT patients.

Methods

This is a retrospective, observational database (Marketscan^®) study. This study included patients ≥18 years old who had auto-HSCT during 2009–2013, had chemotherapy within 60 days prior to auto-HSCT (latest chemotherapy date within the 60 days was the study enrollment date), and had continuous health plan enrollment for at least 365 days before and after the study enrollment date. AP duration was the sum of days supply of all AP prescriptions from 30 days before to 365 days after the study enrollment date. Patients were followed from the study enrollment date to the end of continuous health plan enrollment, death, or December 31, 2014 to assess HZ incidence. The Cox proportional hazards model was used to examine the association between the risk of HZ and AP duration.

Results

This study identified 1959 eligible auto-HSCT patients, of whom 93.0% were prescribed AP. Average AP duration was 220 days (SD = 122), while 200 (11%) patients had AP for ≥1 year. HZ incidence was 42.4/1000 person-years (PY) (95% CI 36.5, 49.0) for the overall auto-HSCT cohort. Among patients who received AP, duration of AP prescriptions and HZ incidence were inversely related. Compared with patients who were on AP for 1–89 days, patients with AP duration of 180–269 days [hazard ratio (HR) = 0.576, p = 0.019], 270–359 days (HR = 0.594, p = 0.023), and ≥360 days (HR = 0.309, p < 0.001) had significantly lower risk of HZ.

Conclusion

Auto-HSCT patients are at increased risk for HZ, even when prescribed AP. A safe and effective vaccine against HZ for auto-HSCT patients could be a useful adjunctive prevention strategy.

http://ift.tt/2qka9wb

Estimation of glomerular filtration rate in cancer patients with abnormal body composition and relation with carboplatin toxicity

Abstract

Purpose

Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft–Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFR_cysC-creat) in cancer patients.

Methods

Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFR_cysC-creat (CKD-EPI creatinine–cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed.

Results

In 131 patients without renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but not with cystatin C (r = −0.07, p = 0.43). In patients with the lowest LBM percentage, the CrCl was significantly higher than GFR_cysC-creat indicating an overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with carboplatin AUC 5 (mg/ml min) ± paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFR_cysC-creat ratio (p = 0.006). By ROC analysis, the CrCl/GFR_cysC-creat ratio threshold predicting severe thrombocytopenia was 1.23.

Conclusions

A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFR_cysC-creat ratio allows the identification of these patients.

http://ift.tt/2pOdTmL

Estimation of glomerular filtration rate in cancer patients with abnormal body composition and relation with carboplatin toxicity

Abstract

Purpose

Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft–Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFR_cysC-creat) in cancer patients.

Methods

Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFR_cysC-creat (CKD-EPI creatinine–cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed.

Results

In 131 patients without renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but not with cystatin C (r = −0.07, p = 0.43). In patients with the lowest LBM percentage, the CrCl was significantly higher than GFR_cysC-creat indicating an overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with carboplatin AUC 5 (mg/ml min) ± paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFR_cysC-creat ratio (p = 0.006). By ROC analysis, the CrCl/GFR_cysC-creat ratio threshold predicting severe thrombocytopenia was 1.23.

Conclusions

A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFR_cysC-creat ratio allows the identification of these patients.

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An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change

Abstract

Background

Simple bone cysts (SBC) have been documented to occur in adults with closed physeal plates, most commonly affecting the calcaneus in this patient subset. Although most authors theorize an association to trauma, etiology of simple bone cysts remains an enigma up to now.

Case presentation

A 26-year-old kickboxing coach sought consult for a painful right shoulder which on radiographs and magnetic resonance (MR) imaging showed a proximal humeral lesion with signs of ossification. The patient was lost to follow-up but again sought consult after 3 years for the recurring complaint. On repeat radiographs, computed tomography (CT) scan, and MR images, tumor enlargement with cystic findings typical of simple bone cyst were documented. Diagnostic aspiration of the lesion was firstly done, revealing straw-colored fluid. The patient then underwent intralesional curettage with alpha-tricalcium phosphate cement reconstruction of the lytic defect. No perioperative complications were incurred, and on latest follow-up at 3 years postoperatively, Musculoskeletal Tumor Society (MSTS) and visual analog scale (VAS) pain scores were 30/30 and 0/10, respectively.

Conclusions

The authors believe their report provides support to a possible association to trauma of simple bone cysts occurring in the adult population with closed physes and suggest this subset of patients may require a different treatment approach from that for juvenile simple bone cysts.

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Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma

Abstract

Purpose

Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma.

Methods

We prospectively evaluated s-p53-Abs levels before and after surgery in 61 patients with extrahepatic cholangiocarcinoma to determine the relationship between clinicopathological factors and the prognostic significance of s-p53-Abs.

Results

Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23% were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) significantly increased the rate of positive extrahepatic cholangiocarcinoma cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs, P = 0.035). There were no significant differences in clinicopathological factors between the p53-seropositive and p53-seronegative patients. An immunohistochemical analysis showed the presence of significant associations between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic factor for the survival in either univariate or multivariate analyses, p53 immunoreactivity was independently associated with a poor survival. Among patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced after surgery in most.

Conclusion

These findings suggested that s-p53-Abs might be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for a diagnosis, but was not useful for predicting tumor recurrence or the survival. This study was registered as UMIN000014530.

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An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change

Abstract

Background

Simple bone cysts (SBC) have been documented to occur in adults with closed physeal plates, most commonly affecting the calcaneus in this patient subset. Although most authors theorize an association to trauma, etiology of simple bone cysts remains an enigma up to now.

Case presentation

A 26-year-old kickboxing coach sought consult for a painful right shoulder which on radiographs and magnetic resonance (MR) imaging showed a proximal humeral lesion with signs of ossification. The patient was lost to follow-up but again sought consult after 3 years for the recurring complaint. On repeat radiographs, computed tomography (CT) scan, and MR images, tumor enlargement with cystic findings typical of simple bone cyst were documented. Diagnostic aspiration of the lesion was firstly done, revealing straw-colored fluid. The patient then underwent intralesional curettage with alpha-tricalcium phosphate cement reconstruction of the lytic defect. No perioperative complications were incurred, and on latest follow-up at 3 years postoperatively, Musculoskeletal Tumor Society (MSTS) and visual analog scale (VAS) pain scores were 30/30 and 0/10, respectively.

Conclusions

The authors believe their report provides support to a possible association to trauma of simple bone cysts occurring in the adult population with closed physes and suggest this subset of patients may require a different treatment approach from that for juvenile simple bone cysts.

http://ift.tt/2pPhlMU