Τρίτη 6 Ιουνίου 2017

Particulate matter air pollution and liver cancer survival

Particulate matter (PM) air pollution exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. Twenty thousand, two hundred and twenty-one California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000 and 2009 were used to examine the effect of exposure to ambient PM with diameter <2.5 μm (PM2.5) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM2.5 to all-cause and liver cancer-specific mortality linearly and nonlinearly—overall and stratified by stage at diagnosis (local, regional and distant)—adjusting for potential individual and geospatial confounders.PM2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all-cause mortality HR associated with a 1 standard deviation (5.0 µg/m3) increase in PM2.5 was 1.18 (95% CI: 1.16–1.20); 1.31 (95% CI:1.26–1.35) for local stage, 1.19 (95% CI:1.14–1.23) for regional stage, and 1.05 (95% CI:1.01–1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer-specific mortality and PM2.5 were slightly attenuated compared to all-cause mortality, but with the same patterns.Exposure to elevated PM2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations.



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Molecular typing of non-polio enteroviruses isolated from acute flaccid paralysis cases in Iran from 2010 to 2015

Abstract



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Molecular typing of non-polio enteroviruses isolated from acute flaccid paralysis cases in Iran from 2010 to 2015

Abstract



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Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control

Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control
Wed, 07 Jun 2017 05:57:03 +0000
Αποτέλεσμα εικόνας για extraglottic tracheal tube
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Emergency front-of-neck access: scalpel or cannula

,The parable of Buridan's ass
Wed, 07 Jun 2017 05:46:05 +0000
Σχετική εικόνα

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

The combination of DEX and OND should be recommended in children with a high risk of POV.......Dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) FOR Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV)

Colorectal cancer metastatic disease progression in Australia: A population-based analysis

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Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Qingwei Luo, Dianne L. O'Connell, Clare Kahn, Xue Qin Yu
BackgroundNo previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.MethodsAll localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000–2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.ResultsAfter a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79years vs <60years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.ConclusionsAn understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients.



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Dual HER2 Blockade Helps Prevent Breast Cancer Return [News in Brief]

The addition of pertuzumab to trastuzumab reduces the incidence of recurrence following surgery.



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Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-grade Ovarian Carcinoma [Research Briefs]

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.



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In vitro antineoplastic effects of brivaracetam and lacosamide on human glioma cells

Epilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistanc...

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The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance



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Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma



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Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies



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Herpes zoster risk after 21 specific cancers: population-based case–control study



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A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases



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Clinical value of R-spondins in triple-negative and metaplastic breast cancers



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Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study



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Pre-diagnosis diet and survival after a diagnosis of ovarian cancer



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Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab



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One-carbon metabolism in cancer



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Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records



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BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses



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Efficacy and safety of gemcitabine plus S-1 in pancreatic cancer: a pooled analysis of individual patient data



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Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer



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GP participation in increasing uptake in a national bowel cancer screening programme: the PEARL project



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Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma



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Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases



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The contribution of body mass index to appraisal delay in colorectal cancer diagnosis: a structural equation modelling study



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Mutation status among patients with sinonasal mucosal melanoma and its impact on survival



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Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study



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The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance



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Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma



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Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies



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Herpes zoster risk after 21 specific cancers: population-based case–control study



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A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases



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Clinical value of R-spondins in triple-negative and metaplastic breast cancers



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Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study



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Pre-diagnosis diet and survival after a diagnosis of ovarian cancer



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Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab



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One-carbon metabolism in cancer



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Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records



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BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses



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Efficacy and safety of gemcitabine plus S-1 in pancreatic cancer: a pooled analysis of individual patient data



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Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer



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GP participation in increasing uptake in a national bowel cancer screening programme: the PEARL project



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Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma



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Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases



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The contribution of body mass index to appraisal delay in colorectal cancer diagnosis: a structural equation modelling study



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Mutation status among patients with sinonasal mucosal melanoma and its impact on survival



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Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study



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A Phase 1 Study of LY2874455, an Oral Selective pan-FGFR Inhibitor, in Patients with Advanced Cancer

Abstract

Background

We report here a phase 1 study of LY2874455, a potent oral selective pan-fibroblast growth factor receptor (FGFR) inhibitor.

Objective

The primary objective was to determine the recommended phase 2 dosing (RP2D). Secondary objectives included determining toxicity, antitumor activity, pharmacokinetics (PK), and pharmacodynamic (PD) properties of LY2874455.

Patients and Methods

This study comprised two parts: (a) dose escalation with 3 + 3 cohorts in patients with solid tumors and (b) dose-expansion cohorts in patients with gastric cancer (GC) and non-small cell lung cancer (NSCLC). Part A: 36 patients in 11 dose cohorts ranging from 2 to 24 mg twice daily (BID). RP2D was 16 mg BID. Part B: GC cohort, 29 patients, NSCLC cohort, 27 patients, all treated at the RP2D.

Results

LY2874455 was slowly absorbed and generally showed linear PK. The effective half-life was ∼12 h. PD properties of LY2874455 occurred at doses ≥10 mg by increases in serum phosphorus. Phosphate binders were administered to control serum phosphorus. LY2874455 was generally well tolerated; most toxicities were grade 1 or 2; most frequent were hyperphosphatemia, diarrhea, and stomatitis. Efficacy: part A: 24 patients evaluable: 1 patient in the 14-mg BID cohort with GC had a partial response (PR); 14 patients had stable disease (SD); part B: NSCLC cohort: 11 of 12 evaluable patients had SD; GC cohort: 15 patients evaluable: 1 patient with PR; 12 patients with SD.

Conclusions

LY2874455 has an RP2D of 16 mg BID and demonstrated good tolerability and activity in solid-organ cancer patients. The role of FGFR inhibition on tumor growth in patients requires further study. (NCT01212107).



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Synthesis and Characterization of Novel BMI1 Inhibitors Targeting Cellular Self-Renewal in Hepatocellular Carcinoma

Abstract

Background

Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types.

Objective

We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC.

Methods

We have recently participated in characterizing the first known pharmacological small molecule inhibitor of BMI1. Here, we synthesized a panel of novel BMI1 inhibitors and examined their ability to alter cellular growth and eliminate cancer progenitor/stem-like cells in HCC with different p53 backgrounds.

Results

Among various molecules examined, RU-A1 particularly downregulated BMI1 expression, impaired cell viability, reduced cell migration, and sensitized HCC cells to 5-fluorouracil (5-FU) in vitro. Notably, long-term analysis of HCC survival showed that, unlike chemotherapy, RU-A1 effectively reduced CSC content, even as monotherapy. BMI1 inhibition with RU-A1 diminished the number of stem-like cells in vitro more efficiently than the model compound C-209, as demonstrated by clonogenic assays and impairment of CSC marker expression. Furthermore, xenograft assays in zebrafish showed that RU-A1 abrogated tumor growth in vivo.

Conclusions

This study demonstrates the ability to identify agents with the propensity for targeting CSCs in HCC that could be explored as novel treatments in the clinical setting.



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A Phase 1 Study of LY2874455, an Oral Selective pan-FGFR Inhibitor, in Patients with Advanced Cancer

Abstract

Background

We report here a phase 1 study of LY2874455, a potent oral selective pan-fibroblast growth factor receptor (FGFR) inhibitor.

Objective

The primary objective was to determine the recommended phase 2 dosing (RP2D). Secondary objectives included determining toxicity, antitumor activity, pharmacokinetics (PK), and pharmacodynamic (PD) properties of LY2874455.

Patients and Methods

This study comprised two parts: (a) dose escalation with 3 + 3 cohorts in patients with solid tumors and (b) dose-expansion cohorts in patients with gastric cancer (GC) and non-small cell lung cancer (NSCLC). Part A: 36 patients in 11 dose cohorts ranging from 2 to 24 mg twice daily (BID). RP2D was 16 mg BID. Part B: GC cohort, 29 patients, NSCLC cohort, 27 patients, all treated at the RP2D.

Results

LY2874455 was slowly absorbed and generally showed linear PK. The effective half-life was ∼12 h. PD properties of LY2874455 occurred at doses ≥10 mg by increases in serum phosphorus. Phosphate binders were administered to control serum phosphorus. LY2874455 was generally well tolerated; most toxicities were grade 1 or 2; most frequent were hyperphosphatemia, diarrhea, and stomatitis. Efficacy: part A: 24 patients evaluable: 1 patient in the 14-mg BID cohort with GC had a partial response (PR); 14 patients had stable disease (SD); part B: NSCLC cohort: 11 of 12 evaluable patients had SD; GC cohort: 15 patients evaluable: 1 patient with PR; 12 patients with SD.

Conclusions

LY2874455 has an RP2D of 16 mg BID and demonstrated good tolerability and activity in solid-organ cancer patients. The role of FGFR inhibition on tumor growth in patients requires further study. (NCT01212107).



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Synthesis and Characterization of Novel BMI1 Inhibitors Targeting Cellular Self-Renewal in Hepatocellular Carcinoma

Abstract

Background

Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types.

Objective

We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC.

Methods

We have recently participated in characterizing the first known pharmacological small molecule inhibitor of BMI1. Here, we synthesized a panel of novel BMI1 inhibitors and examined their ability to alter cellular growth and eliminate cancer progenitor/stem-like cells in HCC with different p53 backgrounds.

Results

Among various molecules examined, RU-A1 particularly downregulated BMI1 expression, impaired cell viability, reduced cell migration, and sensitized HCC cells to 5-fluorouracil (5-FU) in vitro. Notably, long-term analysis of HCC survival showed that, unlike chemotherapy, RU-A1 effectively reduced CSC content, even as monotherapy. BMI1 inhibition with RU-A1 diminished the number of stem-like cells in vitro more efficiently than the model compound C-209, as demonstrated by clonogenic assays and impairment of CSC marker expression. Furthermore, xenograft assays in zebrafish showed that RU-A1 abrogated tumor growth in vivo.

Conclusions

This study demonstrates the ability to identify agents with the propensity for targeting CSCs in HCC that could be explored as novel treatments in the clinical setting.



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Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies?.

Purpose of review: This article reviews the phenomenon of opioid-induced hyperalgesia (OIH) and its implications for clinical anesthesia. The goal of this review is to give an update on perioperative prevention and treatment strategies, based on findings in preclinical and clinical research. Recent findings: Several systems have been suggested to be involved in the pathophysiology of OIH with a focus on the glutaminergic system. Very recently preclinical data revealed that peripheral [mu]-opioid receptors (MORs) are key players in the development of OIH and acute opioid tolerance (AOT). Peripheral MOR antagonists could, thus, become a new prevention/treatment option of OIH in the perioperative setting. Although the impact of OIH on postoperative pain seems to be moderate, recent evidence suggests that increased hyperalgesia following opioid treatment correlates with the risk of developing persistent pain after surgery. In clinical practice, distinction among OIH, AOT and acute opioid withdrawal remains difficult, especially because a specific quantitative sensory test to diagnose OIH has not been validated yet. Summary: Since the immediate postoperative period is not ideal to initiate long-term treatment for OIH, the best strategy is to prevent its occurrence. A multimodal approach, including choice of opioid, dose limitations and addition of nonopioid analgesics, is recommended. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Therapeutic Alliance and Group Cohesion in an Online Support Program for Adolescent and Young Adult Cancer Survivors: Lessons from “Recapture Life”

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Long-Term Follow-up Consultation After Childhood Cancer in the Rhône-Alpes Region of France: Feedback From Adult Survivors and Their General Practitioners

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Adolescent and Young Adult Patients with Cancer: Perceptions of Care

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Therapeutic Alliance and Group Cohesion in an Online Support Program for Adolescent and Young Adult Cancer Survivors: Lessons from “Recapture Life”

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Long-Term Follow-up Consultation After Childhood Cancer in the Rhône-Alpes Region of France: Feedback From Adult Survivors and Their General Practitioners

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Adolescent and Young Adult Patients with Cancer: Perceptions of Care

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Cognitive, neurophysiologic and metabolic sequelae of previous hypoglycemic coma revealed by hyperinsulinemic-hypoglycemic clamp in type 1 diabetic patients

Abstract

To examine the relationship between electroencephalographic (EEG) activity and hypoglycemia unawareness, we investigated early parameters of vigilance and awareness of various symptom categories in response to hypoglycemia in intensively treated type 1 diabetic (T1DM) patients with different degrees of hypoglycemia unawareness. Hypoglycemia was induced with a hyperinsulinemic-hypoglycemic clamp in six T1DM patients with a history of hypoglycemia unawareness previous severe hypoglycemic coma (SH) and in six T1DM patients without (C) history of hypoglycemia unawareness previous severe hypoglycemic coma. Cognitive function tests (four choice reaction time), counterregulatory responses (adrenaline), and symptomatic responses were evaluated at euglycemia (90 mg/dl) and during step-wise plasma glucose reduction (68, 58 and 49 mg/dl). EEG activity was recorded continuously throughout the study and analyzed by spectral analysis. Cognitive function deteriorated significantly at a glucose threshold of 55 ± 1 mg/dl in both groups (p = ns) during hypoglycemia, while the glucose threshold for autonomic symptoms was significantly lower in SH patients than in C patients (49 ± 1 vs. 54 ± 1 mg/dl, p < 0.05, respectively). In SH patients, eye-closed resting EEG showed a correlation between the mean dominance frequency and plasma glucose (r = 0.62, p < 0.001). Theta relative power increased during controlled hypoglycemia compared to euglycemia (21.6 ± 6 vs. 15.5 ± 3% Hz p < 0.05) and was higher than in the C group (21.6 ± 6 vs. 13.8 ± 3%, p < 0.03). The cognitive task beta activity was lower in the SH group than in the C group (14.8 ± 3 Hz, vs. 22.6 ± 4 vs. p < 0.03). Controlled hypoglycemia elicits cognitive dysfunction in both C and SH patients; however, significant EEG alterations during hypoglycemia were detected mainly in patients with a history of hypoglycemia unawareness and previous severe hypoglycemic coma. These data suggest that prior episodes of hypoglycemic coma modulate brain electric activity.



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[Chemotherapy for colorectal cancer: Pragmatic assessment of prescription changes and relative dose intensity].

[Chemotherapy for colorectal cancer: Pragmatic assessment of prescription changes and relative dose intensity].

Bull Cancer. 2017 Jun 01;:

Authors: Thibault V, Leguelinel-Blache G, Obled S, Loriot V, Phouttasang V, Wolf P, Bastide S, Cousin C, Favier M

Abstract
INTRODUCTION: Chemotherapy induced toxicities can generate changes in prescribing and relative dose intensity which have an impact on therapeutic efficacy.
METHOD: This is a prospective observational study performed in hepato-gastroenterology department for 6 months. All patients treated for colorectal cancer and beginning a protocol with at least one parenteral drug have been included.
RESULTS: Among the 48 patients enrolled, 85.4% of them had at least one prescription change, which concerned 30.3% of 238 cycles. Of the 766 analyzed prescription lines, 16.6% of them were postponed and/or 6.7% had modified dosage and/or 5.6% were stopped prematurely. Grades 2 to 4 adverse reactions were responsible for at least one change prescribing to 64.6% of patients and 17.6% of cycles. Toxicity induced prescription changes were mainly due to clinical toxicities (79.3%). The rate of patients with a relative dose intensity greater than 70% was 92.9% in adjuvant state, 66.7% and 62.5% in metastatic state first line and second and subsequent line.
CONCLUSION: High-grade clinical toxicities are the main chemotherapy prescription change pattern in colorectal cancer. Knowledge of toxicities before the patient's arrival is expected to target patients for which the drug preparation can be anticipated and for which a cycle postponement, dose adjustment or discontinuation is necessary.

PMID: 28578823 [PubMed - as supplied by publisher]



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[The economic burden of cancer and the access to innovation should boost the use of real world data].

[The economic burden of cancer and the access to innovation should boost the use of real world data].

Bull Cancer. 2017 Jun;104(6):495-496

Authors: Thierry JP

PMID: 28578773 [PubMed - in process]



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FDA Expands Approval of Pembrolizumab for First-Line Treatment of Non-Small Cell Lung Cancer

FDA approved the immune checkpoint inhibitor pembrolizumab to be used with chemotherapy as a first-line treatment for non-small cell lung cancer.



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ERβ1 inhibits metastasis of androgen receptor-positive triple-negative breast cancer by suppressing ZEB1

Increasing evidence has indicated an important role for estrogen receptor beta 1 (ERβ1) in breast cancer. However, the role of ERβ1 in the metastasis of androgen receptor (AR)-positive triple-negative breast c...

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Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models

Abstract

Background

Doxorubicin (DXR) hydrochloride (HCl) liposome injection is an important part of the treatment armamentarium for a number of cancers. With growing needs for affordable and effective anticancer treatments, the development of generics is becoming increasingly important to facilitate patient access to vital medications. We conducted studies in relevant mouse models of cancer to compare the preclinical antitumour efficacy and plasma pharmacokinetic profile of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceutical Industries Ltd. (SPIL DXR HCl liposome injection) with Caelyx® (reference DXR HCl liposome injection).

Methods

Syngeneic fibrosarcoma (WEHI 164)-bearing BALB/c mice and athymic nude mice transplanted with MX-1 human mammary carcinoma xenografts were treated with SPIL DXR HCl liposome injection, reference DXR HCl liposome injection or placebo, to compare tumour volume, antitumour activity (percentage test/control [%T/C] ratio, tumour regression, and specific tumour growth delay) and toxicity (survival and weight changes) in response to treatment. The pharmacokinetic profile of the SPIL and reference product was also studied in syngeneic fibrosarcoma-bearing mice.

Results

Treatment with either SPIL or reference DXR HCl liposome injection resulted in significant reduction in tumour volume from baseline in both models at all doses tested. High antitumour activity (%T/C ≤ 10) was seen from Day 21 and Day 14 onwards in SPIL and reference DXR HCl liposome injection–treated syngeneic fibrosarcoma-bearing mice, respectively, at 9 mg/kg. Moderate antitumour activity (%T/C ≤ 20) was seen from Day 17 and Day 24 onwards in SPIL and reference DXR HCl liposome injection–treated MX-1-bearing mice, respectively, at 6 mg/kg. No significant differences in tumour volume and %T/C were observed between SPIL and reference DXR HCl liposome injection–treated groups at any dose (p ≥ 0.05). Toxicity profiles were considered to be generally comparable. Evaluation of test/reference (A/B) ratios and 90% confidence intervals (CIs) for peak serum concentration (Cmax) and area under the curve (AUC0-t, and AUC0-∞) demonstrated bioequivalence of SPIL and reference DXR HCl liposome injections.

Conclusions

Establishing similarity is of critical importance during the development of generic treatments. SPIL and reference DXR HCl liposome injections were shown to be comparable with regards to antitumour activity, toxicity and pharmacokinetics.



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Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma

Abstract

Background

Deregulations of long non-coding RNAs (lncRNAs) have been implicated in cancer initiation and progression. Current methods can only capture differential expression of lncRNAs at the population level and ignore the heterogeneous expression of lncRNAs in individual patients.

Methods

We propose a method (LncRIndiv) to identify differentially expressed (DE) lncRNAs in individual cancer patients by exploiting the disrupted ordering of expression levels of lncRNAs in each disease sample in comparison with stable normal ordering. LncRIndiv was applied to lncRNA expression profiles of lung adenocarcinoma (LUAD). Based on the expression profile of LUAD individual-level DE lncRNAs, we used a forward selection procedure to identify prognostic signature for stage I-II LUAD patients without adjuvant therapy.

Results

In both simulated data and real pair-wise cancer and normal sample data, LncRIndiv method showed good performance. Based on the individual-level DE lncRNAs, we developed a robust prognostic signature consisting of two lncRNA (C1orf132 and TMPO-AS1) for stage I-II LUAD patients without adjuvant therapy (P = 3.06 × 10−6, log-rank test), which was confirmed in two independent datasets of GSE50081 (P = 1.82 × 10−2, log-rank test) and GSE31210 (P = 7.43 × 10−4, log-rank test) after adjusting other clinical factors such as smoking status and stages. Pathway analysis showed that TMPO-AS1 and C1orf132 could affect the prognosis of LUAD patients through regulating cell cycle and cell adhesion.

Conclusions

LncRIndiv can successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.



http://ift.tt/2qXV5G9

Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma

Abstract

Background

Deregulations of long non-coding RNAs (lncRNAs) have been implicated in cancer initiation and progression. Current methods can only capture differential expression of lncRNAs at the population level and ignore the heterogeneous expression of lncRNAs in individual patients.

Methods

We propose a method (LncRIndiv) to identify differentially expressed (DE) lncRNAs in individual cancer patients by exploiting the disrupted ordering of expression levels of lncRNAs in each disease sample in comparison with stable normal ordering. LncRIndiv was applied to lncRNA expression profiles of lung adenocarcinoma (LUAD). Based on the expression profile of LUAD individual-level DE lncRNAs, we used a forward selection procedure to identify prognostic signature for stage I-II LUAD patients without adjuvant therapy.

Results

In both simulated data and real pair-wise cancer and normal sample data, LncRIndiv method showed good performance. Based on the individual-level DE lncRNAs, we developed a robust prognostic signature consisting of two lncRNA (C1orf132 and TMPO-AS1) for stage I-II LUAD patients without adjuvant therapy (P = 3.06 × 10−6, log-rank test), which was confirmed in two independent datasets of GSE50081 (P = 1.82 × 10−2, log-rank test) and GSE31210 (P = 7.43 × 10−4, log-rank test) after adjusting other clinical factors such as smoking status and stages. Pathway analysis showed that TMPO-AS1 and C1orf132 could affect the prognosis of LUAD patients through regulating cell cycle and cell adhesion.

Conclusions

LncRIndiv can successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.



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Disseminated and late metastatic disease from nasal pit leiomyosarcoma after radical surgical resection. Case report of a singular presentation of a rare disease

Abstract

Background

Leiomyosarcoma of the head and neck is a rare cancer with high local aggressiveness. Radical surgery and adjuvant treatment offer the best chance for cure, nonetheless 5-years recurrence rate remains high. Despite international guidelines are available for soft tissue sarcomas, no recommendations are specifically endorsed for leiomyosarcoma of the head and neck, due to the rarity of its presentation and consequently scarcity of data on long-term outcome.

Case presentation

A 50-year old woman, operated 10 years before for leiomyosarcoma of the nasal pit and with negative 5-years follow-up, was admitted to our ward for impairment of the hepatic function. Total-body CT scan detected multiple localizations at lungs, kidneys, pancreas, bones, muscles, lymph nodes and thyroid. The pathologic report after lung biopsy confirmed the diagnosis of metastasis from leiomyosarcoma and the patients was scheduled for first line chemo-radiotherapy.

Conclusions

Despite adequate primary treatment, distant and disseminated metastatic disease may be not excluded in leiomyosarcoma of the head and neck.



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Squamous cell carcinoma associated with inverted papilloma : Inverted papilloma is a benign, locally aggressive neoplasm that arises in the nasal cavity and is associated with squamous cell carcinoma in approximately 5% of patients.

http://ent-crete.blogspot.com/2017/06/inverted-papilloma-is-benign-locally.html

Squamous cell carcinoma associated with inverted papilloma of the maxillary sinus: our experience with 21 patients

MS Yu, WS Lim, BJ Lee, YS Chung - Clinical Otolaryngology, 2017 - Wiley Online Library
Methods We retrospectively analysed the records of 117 patients with SCC of the maxillary 
sinus who had been treated at Asan Medical Center between 1990 and 2014. SCC of the 
maxillary sinus was histologically confirmed in all patients. Of these 117 patients, 31 were 
excluded because of unidentified primary tumour sites or inadequate follow-up data. 
According to the final pathological diagnosis, patients with IP-associated SCC were ...

quamous cell carcinoma associated with inverted papilloma of the maxillary sinus: our experience with 21 patients

MS Yu, WS Lim, BJ Lee, YS Chung - Clinical Otolaryngology, 2017 - Wiley Online Library
Methods We retrospectively analysed the records of 117 patients with SCC of the maxillary 
sinus who had been treated at Asan Medical Center between 1990 and 2014. SCC of the 
maxillary sinus was histologically confirmed in all patients. Of these 117 patients, 31 were 

Inverted papilloma with associated carcinoma of the nasal cavity and paranasal sinuses: treatment outcomes

G Buiret, X Montbarbon, B Fleury, M Poupart… - Acta oto- …, 2012 - Taylor & Francis
Abstract Conclusions: Degenerated inverted papilloma is a rare, aggressive, and lethal 
disease. To avoid missing the target, it is absolutely necessary to consider the microscopic 
extension even in cases of complete exeresis and to irradiate the whole of the adjacent 

鼻内翻性乳头状瘤恶变 32 例临床分析

于焕新, 刘钢 - 中华耳鼻咽喉头颈外科杂志, 2013 - 万方数据资源系统
目的探讨伴有恶变的鼻腔鼻窦内翻性乳头状瘤(sinonasal inverted papilloma, SNIP) 
的临床特征和组织病理学特征以及影响预后的因素. 方法回顾性分析1991 年1 月至2008 年1 
月32 例SNIP 伴有恶变病例的临床特征以及组织病理学特征. 包括年龄, 性别, 发病部位, 

[HTML] Malignant transformation of sinonasal inverted papilloma: A retrospective analysis of 32 cases

HX Yu, G Liu - Oncology letters, 2014 - spandidos-publications.com
Abstract Sinonasal inverted papillomas (SNIPs) are derived from the benign tumors of the 
epithelial cells and have the potential to recur and exhibit malignant characteristics. The aim 
of the present study was to investigate the clinicopathological features and prognosis of 

Clinical and histologic features of inverted papilloma–associated malignancy

JW Choi, SG KimYM Kim, YH Yoon, AY Kim… - European Archives of …, 2012 - Springer
Abstract The objectives of the study were to analyze the clinical features of inverted 
papillomas (IP) associated with malignancy and to evaluate the correlation of tumor stage, 
survival and histolologic features. We conducted a retrospective review of 18 IP associated 

鼻内翻性乳头状瘤恶变的内镜或内镜辅助下手术

孙伟元, 赵娜, 翟瑞华, 马智军 - 中华耳鼻咽喉头颈外科杂志, 2011 - cqvip.com
目的探讨鼻内镜下或内镜辅助下鼻内翻性乳头状瘤(sinonasal inverted papilloma, Sip) 
恶变的手术方法, 并对其预后及影响因素进行分析. 方法对2001 年2 月至2010 年12 
月山东省潍坊市益都中心医院耳鼻咽喉头颈外科收治的7 例SIP 恶变者于鼻内镜下或内镜辅助下

Inverted papilloma of the nasal cavity and paranasal sinuses: a Korean multicenter study

DY Kim, SL Hong, CH Lee, HR Jin, JM Kang… - The …, 2012 - Wiley Online Library
Methods: In total, 939 patients diagnosed with sinonasal IP treated between 1998 and 2007 
at 17 university hospitals were enrolled. Demographic data and information about previous 
surgeries, the origin and involved site of the tumor, the surgical approach, follow-up 

鼻内镜下手术治疗鼻腔, 鼻窦内翻性乳头状瘤的临床观察及护理

郭虹, 张丹 - 护士进修杂志, 2014 - cqvip.com
目的探讨鼻内镜下手术治疗鼻腔, 鼻窦内翻性乳头状瘤(NIP) 的临床效果. 方法对本院2009 年2 
月~ 2012 年2 月采用鼻内镜手术治疗NIP 的51 例患者的临床资料进行回顾性分析, 并进行2 
年术后跟踪随访, 观察其临床治疗效果. 结果51 例患者无一例术后发生脑脊液鼻漏, 复视, 

鼻内镜联合鼻外径路在鼻腔鼻窦内翻性乳头状瘤手术中的应用

戴艳红, 高下, 丁小琼, 陈峰 - 山東大學耳鼻喉眼學報, 2006 - airitilibrary.com
目的: 探讨鼻内镜联合鼻外径路手术能否降低鼻腔鼻窦内翻性乳头状瘤术后的复发率. 方法: 
将我科2000 年1 月至2006 年1 月收治的鼻腔鼻窦内翻性乳头状瘤且随访资料完整的病例分成
两个阶段(2000 年1 月至2003 年1 月, 2003 年1 月至2006 年1 月) 行回顾性分析: 

鼻内镜下治疗鼻内翻性乳头状瘤的应用价值

陈小林, 陈佳, 李伟, 孙苏光 - 重庆医学, 2013 - cqvip.com
目的探讨鼻内镜手术切除鼻内翻性乳头瘤(NIP) 的临床应用价值. 方法38 例鼻内镜手术切除NIP 
为内镜组, 22 例开放式手术切除NIP 为对照组. 比较两组患者术后并发症, 手术时间, 
手术疗效及复发情况. 结果内镜组共发生并发症12 例(31.6%) 略低于对照组12 例(54.5%), 


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Exosome-derived miR-25-3p and miR-92a-3p stimulate liposarcoma progression

Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.

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Micronuclei frequency in tumors is a predictive biomarker for genetic instability and sensitivity to the DNA repair inhibitor AsiDNA

Therapeutic strategies targeting DNA repair pathway defects have been widely explored, but often only benefit small numbers of patients. Here we characterized potential predictive biomarkers for treatment with AsiDNA, a novel first-in-class DNA repair inhibitor. We evaluated genetic instability and DNA repair defects by direct and indirect assays in 12 breast cancer cell lines to estimate the spontaneous occurrence of single-strand and double-strand breaks (DSB). For each cell line, we monitored constitutive poly(ADP-ribose) polymerase (PARP) activation, spontaneous DNA damage by alkaline comet assay, basal micronuclei (MN) levels, the number of large-scale chromosomal rearrangements (LST), and the status of several DNA repair pathways by transcriptome and genome analysis. Sensitivity to AsiDNA was associated with a high spontaneous frequency of cells with MN and LST and specific alterations in DNA repair pathways that essentially monitor DSB repair defects. A high basal level of MN as a predictive biomarker for AsiDNA treatment was validated in 43 tumor cell lines from various tissues and 15 models of cell- and patient-derived xenografts. MN quantification was also possible in patient biopsies. Overall, this study identified genetic instability as a predictive biomarker for sensitivity to AsiDNA treatment. That MN frequency can be measured in biopsies and does not reveal the same genetic instability as conventional genome assays opens new perspectives for refining the classification of tumors with genetic instability.

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Teaching laboratory management and quality assurance/quality improvement skills in a cytopathology fellowship program



from Cancer via ola Kala on Inoreader http://ift.tt/2s0hOBD
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Exosome-derived miR-25-3p and miR-92a-3p stimulate liposarcoma progression

Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.

http://ift.tt/2s0vJHU

Micronuclei frequency in tumors is a predictive biomarker for genetic instability and sensitivity to the DNA repair inhibitor AsiDNA

Therapeutic strategies targeting DNA repair pathway defects have been widely explored, but often only benefit small numbers of patients. Here we characterized potential predictive biomarkers for treatment with AsiDNA, a novel first-in-class DNA repair inhibitor. We evaluated genetic instability and DNA repair defects by direct and indirect assays in 12 breast cancer cell lines to estimate the spontaneous occurrence of single-strand and double-strand breaks (DSB). For each cell line, we monitored constitutive poly(ADP-ribose) polymerase (PARP) activation, spontaneous DNA damage by alkaline comet assay, basal micronuclei (MN) levels, the number of large-scale chromosomal rearrangements (LST), and the status of several DNA repair pathways by transcriptome and genome analysis. Sensitivity to AsiDNA was associated with a high spontaneous frequency of cells with MN and LST and specific alterations in DNA repair pathways that essentially monitor DSB repair defects. A high basal level of MN as a predictive biomarker for AsiDNA treatment was validated in 43 tumor cell lines from various tissues and 15 models of cell- and patient-derived xenografts. MN quantification was also possible in patient biopsies. Overall, this study identified genetic instability as a predictive biomarker for sensitivity to AsiDNA treatment. That MN frequency can be measured in biopsies and does not reveal the same genetic instability as conventional genome assays opens new perspectives for refining the classification of tumors with genetic instability.

http://ift.tt/2szLoe6

Teaching laboratory management and quality assurance/quality improvement skills in a cytopathology fellowship program



http://ift.tt/2s0hOBD

Chronic myeloid leukemia: Global impact from a local laboratory

The arrival of tyrosine kinase inhibitors forever changed the treatment and outlook of chronic myeloid leukemia. However, most of the world's chronic myeloid leukemia patients live in economically challenged areas and have extremely limited access to the tyrosine kinase inhibitors and diagnostic assays needed to treat chronic myeloid leukemia. What can be done?



http://ift.tt/2s0xWDl

Chronic myeloid leukemia: Global impact from a local laboratory

The arrival of tyrosine kinase inhibitors forever changed the treatment and outlook of chronic myeloid leukemia. However, most of the world's chronic myeloid leukemia patients live in economically challenged areas and have extremely limited access to the tyrosine kinase inhibitors and diagnostic assays needed to treat chronic myeloid leukemia. What can be done?



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Is there progress in the treatment of high-risk myeloma?

Summary

Treatment of high-risk patients is a major challenge in multiple myeloma (MM). Median survival rates of these patients remain poor at about 2 years and there were no major improvements with the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). This resulted in a remarkable discrepancy in the treatment results of MM, with a significant proportion of patients achieving long-term progression-free survival of >10 years (or even cure) while in patients with aggressive disease no or only minor improvements have been achieved. Current consensus statements define high-risk based on International Staging System (ISS) stage III plus the presence of cytogenetic aberrations (t(4;14) and/or del17p) and/or high lactate dehydrogenase (LDH). Regarding the treatment of high-risk patients, autologous stem cell transplantation remains the standard of care in transplant-eligible candidates. However, there is an unmet need for novel therapeutic strategies to overcome the limitations of current treatment modalities. Hence, efforts to study high-risk disease in MM were recently intensified. The ongoing search for new treatment strategies and drug targets is also reflected by the growing number of studies investigating high-risk disease. This short review aims to provide an overview about the current research landscape and recent progress in high-risk MM based on selected abstracts of the ASH 2016 meeting.



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Is there progress in the treatment of high-risk myeloma?

Summary

Treatment of high-risk patients is a major challenge in multiple myeloma (MM). Median survival rates of these patients remain poor at about 2 years and there were no major improvements with the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). This resulted in a remarkable discrepancy in the treatment results of MM, with a significant proportion of patients achieving long-term progression-free survival of >10 years (or even cure) while in patients with aggressive disease no or only minor improvements have been achieved. Current consensus statements define high-risk based on International Staging System (ISS) stage III plus the presence of cytogenetic aberrations (t(4;14) and/or del17p) and/or high lactate dehydrogenase (LDH). Regarding the treatment of high-risk patients, autologous stem cell transplantation remains the standard of care in transplant-eligible candidates. However, there is an unmet need for novel therapeutic strategies to overcome the limitations of current treatment modalities. Hence, efforts to study high-risk disease in MM were recently intensified. The ongoing search for new treatment strategies and drug targets is also reflected by the growing number of studies investigating high-risk disease. This short review aims to provide an overview about the current research landscape and recent progress in high-risk MM based on selected abstracts of the ASH 2016 meeting.



http://ift.tt/2qYa0QH

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients

Abstract

Purpose

The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients.

Materials and methods

A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction.

Results

The median follow-up was 16 months (range, 1–70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022).

Conclusion

This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.



http://ift.tt/2szGaPt

Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells

Abstract

PURPOSE

The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro.

RESULTS

Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83 phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs.

CONCLUSIONS

We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination.



http://ift.tt/2s00JYG

Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy

Abstract

Purpose

To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features.

Methods

We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups.

Results

Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1–2] year-interval by 10.1% and [3–4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1–2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1–4, in colon cancer and in stage III but without impact in rectal cancer and stage II.

Conclusion

Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.



http://ift.tt/2sztAzI

Bone marrow fibrosis at diagnosis predicts survival for primary acute myeloid leukemia

Abstract

Purpose

As a desmoplastic reaction, tissue fibrosis played crucial roles in solid tumor progression, chemo-resistance, and consequently heralded poor clinical outcome. Previous studies implied the effects of marrow fibrosis on prognosis for acute lymphoblastic leukemia were disputable. In this study, we aimed to investigate the potential role of bone marrow fibrosis on clinical survival in acute myeloid leukemia (AML) patients.

Methods

Bone marrow fibrosis (evaluated as reticulin fiber density, RFD) in bone marrow sections was evaluated at diagnosis via computer technology. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of RFD for relapse and survival status. Kaplan–Meier method was used to estimate survival rates per subgroup between patients with different RFD. Cox proportional hazard regression was used to model the overall survival.

Results

High RFD at diagnosis in bone marrow sections from primary AML might predict early relapse and shorter survival (P = 0.003 and 0.001, respectively). The optimal cutoff value of RFD at diagnosis was determined to be 7.2%. Furthermore, the Kaplan–Meier analysis indicated that patients with high marrow RFD had shorter relapse-free survival (RFS) and overall survival (OS) than patients with low RFD (P = 0.007 and 0.000, respectively). Multivariate analysis suggested that similar with cytogenetics, marrow RFD at diagnosis was an independent prognostic factor for RFS [HR 0.564, 95% confidence interval (CI) 0.338–0.940, P = 0.028] and OS (HR 0.457, 95% CI 0.225–0.929, P = 0.031) in primary AML patients.

Conclusions

Our data suggest that marrow RFD before treatment should be seemed as prognostic factor in primary AML, it may provide valuable clues for developing new targeted therapy.



http://ift.tt/2s00JIa

Overexpression of dishevelled 2 is involved in tumor metastasis and is associated with poor prognosis in hepatocellular carcinoma

Abstract

Purpose

Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear.

Methods

Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion.

Results

Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling.

Conclusions

Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.



http://ift.tt/2szZrRc

SLC14A1: a novel target for human urothelial cancer

Abstract

Urinary bladder cancer is the second commonly diagnosed genitourinary malignancy. Previously, bio-molecular alterations have been observed within certain locations such as chromosome 9, retinoblastoma gene and fibroblast growth factor receptor-3. Solute carrier family 14 member 1 (SLC14A1) gene encodes the type-B urea transporter (UT-B) which facilitates the passive movement of urea across cell membrane, and has recently been related with human malignancies, especially for bladder cancer. Herein, we discussed the SLC14A1 gene and UT-B protein properties, aiming to elucidate the expression behavior of SLC14A1 in human bladder cancer. Furthermore, by reviewing some well-established theories regarding the carcinogenesis of bladder cancer, including several genome wide association researches, we have bridged the mechanisms of cancer development with the aberrant expression of SLC14A1. In conclusion, the altered expression of SLC14A1 gene in human urothelial cancer may implicate its significance as a novel target for research.



http://ift.tt/2s07r0r

Comparative efficacy and toxicity of induction chemotherapy with concurrent stereotactic body radiotherapy and stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma

Abstract

Purpose

We compared the clinical efficacy and toxicity of stereotactic body radiotherapy with induction chemotherapy and concurrent radiochemotherapy vs stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma.

Methods

We retrospectively analyzed 38 patients with c-stage T1-3N0M0 non-small cell lung carcinoma who received stereotactic body radiotherapy. All patients received six cycles of chemotherapy. Fifteen of the patients were treated with three cycles of induction chemotherapy, one cycle of concurrent radiochemotherapy, and then two cycles of consolidation chemotherapy, while 23 patients received Sequential Radiotherapy/Chemotherapy.

Results

Patients in the induction chemotherapy group experienced a longer duration of esophagitis (median 2 vs 0, range 0–6 vs 0–3.6 weeks, p = 0.04). We divided the patients into two groups based on their median pre-treatment tumor volume (cm3): >32.11 and ≤32.11. The tumor response rate in patients with larger tumor volume was substantially higher in the induction chemotherapy group than in the Sequential Radiotherapy/Chemotherapy group (66.67 vs 40%). Among patients with pre-treatment tumor volume (cm3) >32.11, the median local progression-free survival (LPFS) in the induction chemotherapy group and Sequential Radiotherapy/Chemotherapy group was 18 months (range 7–72 months) and 11 months (range 6–53 months), respectively. There was a statistically significant difference between the two groups (p = 0.006).

Conclusions

Simultaneous SBRT and chemotherapy can result in a longer duration of esophagitis. However, for patients with large tumor volume, ICT combined with concurrent radiochemotherapy may result in better local tumor response as well as longer LPFS and progression-free survival. To better elucidate the best treatment, further clinical trials are needed.



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Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients

Abstract

Purpose

The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients.

Materials and methods

A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction.

Results

The median follow-up was 16 months (range, 1–70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022).

Conclusion

This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.



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Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells

Abstract

PURPOSE

The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro.

RESULTS

Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83 phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs.

CONCLUSIONS

We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination.



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Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy

Abstract

Purpose

To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features.

Methods

We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups.

Results

Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1–2] year-interval by 10.1% and [3–4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1–2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1–4, in colon cancer and in stage III but without impact in rectal cancer and stage II.

Conclusion

Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.



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Bone marrow fibrosis at diagnosis predicts survival for primary acute myeloid leukemia

Abstract

Purpose

As a desmoplastic reaction, tissue fibrosis played crucial roles in solid tumor progression, chemo-resistance, and consequently heralded poor clinical outcome. Previous studies implied the effects of marrow fibrosis on prognosis for acute lymphoblastic leukemia were disputable. In this study, we aimed to investigate the potential role of bone marrow fibrosis on clinical survival in acute myeloid leukemia (AML) patients.

Methods

Bone marrow fibrosis (evaluated as reticulin fiber density, RFD) in bone marrow sections was evaluated at diagnosis via computer technology. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of RFD for relapse and survival status. Kaplan–Meier method was used to estimate survival rates per subgroup between patients with different RFD. Cox proportional hazard regression was used to model the overall survival.

Results

High RFD at diagnosis in bone marrow sections from primary AML might predict early relapse and shorter survival (P = 0.003 and 0.001, respectively). The optimal cutoff value of RFD at diagnosis was determined to be 7.2%. Furthermore, the Kaplan–Meier analysis indicated that patients with high marrow RFD had shorter relapse-free survival (RFS) and overall survival (OS) than patients with low RFD (P = 0.007 and 0.000, respectively). Multivariate analysis suggested that similar with cytogenetics, marrow RFD at diagnosis was an independent prognostic factor for RFS [HR 0.564, 95% confidence interval (CI) 0.338–0.940, P = 0.028] and OS (HR 0.457, 95% CI 0.225–0.929, P = 0.031) in primary AML patients.

Conclusions

Our data suggest that marrow RFD before treatment should be seemed as prognostic factor in primary AML, it may provide valuable clues for developing new targeted therapy.



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Overexpression of dishevelled 2 is involved in tumor metastasis and is associated with poor prognosis in hepatocellular carcinoma

Abstract

Purpose

Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear.

Methods

Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion.

Results

Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling.

Conclusions

Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.



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SLC14A1: a novel target for human urothelial cancer

Abstract

Urinary bladder cancer is the second commonly diagnosed genitourinary malignancy. Previously, bio-molecular alterations have been observed within certain locations such as chromosome 9, retinoblastoma gene and fibroblast growth factor receptor-3. Solute carrier family 14 member 1 (SLC14A1) gene encodes the type-B urea transporter (UT-B) which facilitates the passive movement of urea across cell membrane, and has recently been related with human malignancies, especially for bladder cancer. Herein, we discussed the SLC14A1 gene and UT-B protein properties, aiming to elucidate the expression behavior of SLC14A1 in human bladder cancer. Furthermore, by reviewing some well-established theories regarding the carcinogenesis of bladder cancer, including several genome wide association researches, we have bridged the mechanisms of cancer development with the aberrant expression of SLC14A1. In conclusion, the altered expression of SLC14A1 gene in human urothelial cancer may implicate its significance as a novel target for research.



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Comparative efficacy and toxicity of induction chemotherapy with concurrent stereotactic body radiotherapy and stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma

Abstract

Purpose

We compared the clinical efficacy and toxicity of stereotactic body radiotherapy with induction chemotherapy and concurrent radiochemotherapy vs stereotactic body radiotherapy with subsequent chemotherapy in patients with clinical stage T1-3N0M0 non-small cell lung carcinoma.

Methods

We retrospectively analyzed 38 patients with c-stage T1-3N0M0 non-small cell lung carcinoma who received stereotactic body radiotherapy. All patients received six cycles of chemotherapy. Fifteen of the patients were treated with three cycles of induction chemotherapy, one cycle of concurrent radiochemotherapy, and then two cycles of consolidation chemotherapy, while 23 patients received Sequential Radiotherapy/Chemotherapy.

Results

Patients in the induction chemotherapy group experienced a longer duration of esophagitis (median 2 vs 0, range 0–6 vs 0–3.6 weeks, p = 0.04). We divided the patients into two groups based on their median pre-treatment tumor volume (cm3): >32.11 and ≤32.11. The tumor response rate in patients with larger tumor volume was substantially higher in the induction chemotherapy group than in the Sequential Radiotherapy/Chemotherapy group (66.67 vs 40%). Among patients with pre-treatment tumor volume (cm3) >32.11, the median local progression-free survival (LPFS) in the induction chemotherapy group and Sequential Radiotherapy/Chemotherapy group was 18 months (range 7–72 months) and 11 months (range 6–53 months), respectively. There was a statistically significant difference between the two groups (p = 0.006).

Conclusions

Simultaneous SBRT and chemotherapy can result in a longer duration of esophagitis. However, for patients with large tumor volume, ICT combined with concurrent radiochemotherapy may result in better local tumor response as well as longer LPFS and progression-free survival. To better elucidate the best treatment, further clinical trials are needed.



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The surgical outcomes of lung cancer combined with interstitial pneumonia: a single-institution report

Abstract

Purpose

Several studies have reported that an acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection in patients with non-small cell lung cancer (NSCLC); however, the perioperative management strategy is controversial.

Methods

The data of lung cancer patients at Nagasaki University Hospital from June 1994 to October 2013 were retrospectively reviewed.

Results

Among all 1701 NSCLC patients who underwent lung resection, 59 (3.5%) had IIP. Five patients (8.5%) had an AE of IIP following lung resection, three (60%) of whom died in hospital. Univariate and multivariate analyses were performed to identify possible risk factors for AE. The univariate analyses identified LDH and the volume of blood loss as risk factors. The multivariate analysis identified no factors. The treatment for an AE included steroid pulse therapy and neutrophil elastase inhibitor therapy. Direct hemoperfusion with polymyxin B immobilized the fiber column and immunosuppressant therapy was attempted in some of the patients who did not respond to these treatments.

Conclusion

Patients with lung cancer and IIP have a higher risk of chest surgery and a poor prognosis. Very careful surgery and perioperative management are needed, because AEs are often difficult to AE predict.



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The surgical outcomes of lung cancer combined with interstitial pneumonia: a single-institution report

Abstract

Purpose

Several studies have reported that an acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection in patients with non-small cell lung cancer (NSCLC); however, the perioperative management strategy is controversial.

Methods

The data of lung cancer patients at Nagasaki University Hospital from June 1994 to October 2013 were retrospectively reviewed.

Results

Among all 1701 NSCLC patients who underwent lung resection, 59 (3.5%) had IIP. Five patients (8.5%) had an AE of IIP following lung resection, three (60%) of whom died in hospital. Univariate and multivariate analyses were performed to identify possible risk factors for AE. The univariate analyses identified LDH and the volume of blood loss as risk factors. The multivariate analysis identified no factors. The treatment for an AE included steroid pulse therapy and neutrophil elastase inhibitor therapy. Direct hemoperfusion with polymyxin B immobilized the fiber column and immunosuppressant therapy was attempted in some of the patients who did not respond to these treatments.

Conclusion

Patients with lung cancer and IIP have a higher risk of chest surgery and a poor prognosis. Very careful surgery and perioperative management are needed, because AEs are often difficult to AE predict.



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