Cardiac output response to exercise in patients before allogenic hematopoietic stem cell transplantation

Abstract

Introduction

High-dose chemotherapy for remission induction can induce cardiac toxicity prior to hematopoietic stem cell transplantation (HSCT). However, the details of cardiac function in patients undergoing HSCT are unclear, particularly during exercise. The aim of present study was to evaluate cardiac output responses to exercise in patients after high-dose chemotherapy before HSCT compared with in age-matched healthy controls.

Methods

Twenty-nine patients before HSCT (age 44.6 ± 15.2 years) and 13 controls (45.8 ± 16.0 years) performed the 6-min walk test (6MWT). Cardiac output (CO), stroke volume (SV), heart rate (HR), and cardiac index (CI) were continuously measured during the 6MWT using the noninvasive thoracic impedance method.

Results

No significant difference was observed in the six-minute walk distance (6MD) between the two groups. SV, CO, and CI both at rest and the end of the 6MWT in the patients were significantly lower, compared with the controls, but there was no significant difference in HR. In all subjects, the 6MD was positively correlated with SV, CO, CI, and HR after the 6MWT.

Conclusion

These findings suggest that cardiac output response to exercise indicates exercise intolerance, which may not be detected by 6MD in patients before HSCT.

https://ift.tt/2lVM3Vp

Targeting tumor-associated acidity in cancer immunotherapy

Abstract

Checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1) monoclonal antibodies have changed profoundly the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and bladder cancer. Currently, they are tested in various tumor entities as monotherapy or in combination with chemotherapies or targeted therapies. However, only a subgroup of patients benefit from checkpoint blockade (combinations). This raises the question, which all mechanisms inhibit T cell function in the tumor environment, restricting the efficacy of these immunotherapeutic approaches. Serum activity of lactate dehydrogenase, likely reflecting the glycolytic activity of the tumor cells and thus acidity within the tumor microenvironment, turned out to be one of the strongest markers predicting response to checkpoint inhibition. In this review, we discuss the impact of tumor-associated acidity on the efficacy of T cell-mediated cancer immunotherapy and possible approaches to break this barrier.

https://ift.tt/2Nt4Vr9

Dose-reduced first cycle of chemotherapy for prevention of life-threatening acute complications in nonseminomatous germ cell tumor patients with ultra high tumor markers and/or poor performance status

Abstract

Purpose

Patients with metastatic nonseminomatous germ cell tumors (mNSGCT) and a high tumor burden or a poor performance status at initial diagnosis are at risk from potentially life-threatening early complications during or after the first chemotherapy cycle. The outcomes with dose-reduced first cycle of chemotherapy in this population of patients are not well established.

Methods

We performed a retrospective analysis of patients with mNSGCT and International Germ Cell Cancer Collaborative Group (IGCCCG) poor risk features. All patients received cisplatin and etoposide-based combinations as first-line treatment. Ultra high tumor marker levels were defined as α-fetoprotein ≥ 100,000 ng/ml or human chorionic gonadotropin ≥ 200,000 mIU/ml. Before 2005, the first treatment cycle was administered at a full dose in our center. After 2005, we used an abbreviated course of cisplatin and etoposide (EP) for the first cycle, followed by subsequent full-dose administration.

Results

From 1987 to 2012, 265 patients with poor risk features according to IGCCCG received first-line chemotherapy. Among them, 63 out of 265 (24%) patients had ultra high tumor marker levels and/or ECOG performance status of 3–4. Dose reduction of the first chemotherapy cycle was associated with a significant decrease of life-threatening complications from 76 to 44% (p = 0.01), but not with the overall survival (HR 0.99, 95% CI 0.44–2.26).

Conclusions

Dose reduction of the first EP cycle by 40–60% in the subgroup of poor risk patients with ultra high tumor marker levels and/or ECOG performance status 3–4 is associated with significantly lowered acute complication rates but not with overall survival.

https://ift.tt/2KPA1aL

Up-regulated lncRNA AFAP1-AS1 indicates a poor prognosis and promotes carcinogenesis of breast cancer

Abstract

Background

Long noncoding RNAs (lncRNAs) have been reported to play crucial roles in breast cancer. This study aimed to determine the clinical significance and biological functions of lncRNA AFAP1-AS1 in breast cancer.

Methods

The expression of AFAP1-AS1 in breast cancer tissue and adjacent normal tissue from 160 patients and breast cancer cell lines were determined by qRT-PCR. The clinical characteristics of patients were collected to analyse the correlation between AFAP1-AS1 expression and malignancy status. Kaplan–Meier and Cox proportional hazards model were used to analyze whether AFAP1-AS1 expression impacted prognosis. To assess the effect of AFAP1-AS1 on MCF-7 cells proliferation, cell viability, EdU incorporation and colony formation assays were conducted after AFAP1-AS1 knockdown by siRNA. The apoptosis was detected by Caspase-3 activity, cell cycle analysis, Bcl-2 and Bax protein expression. Wound scratch assay and EMT-related protein expression (E-cadherin, N-cadherin and Vimentin) were conducted to evaluate the metastasis ability. To further determine the effect of AFAP1-AS1 on AFAP1, the mRNA and protein expression of AFAP1 and subsequent actin filament integrity were measured after AFAP1-AS1 knockdown.

Results

The expression of AFAP1-AS1 was up-regulated in human breast cancer tissue and associated with malignancy status, high expression of AFAP1-AS1 had a poor prognosis in breast cancer patients. AFAP1-AS1 expression was up-regulated in 4 breast cancer cell lines (MCF-7, SK-RB-3, MDA-MB-231and MDA-MB-468) compared with normal breast cell line HBL-100. MCF-7, the most up-regulation cancer cell, was used for following studies. AFAP1-AS1 knockdown can inhibit the proliferation, metastasis and promote apoptosis of MCF-7. However, the AFAP1 expression and actin filament integrity was not affected after AFAP1-AS1 knockdown.

Conclusion

Up-regulated lncRNA AFAP1-AS1 indicates a poor prognosis in breast cancer patients and regulated the breast cancer cells proliferation, apoptosis and metastasis.

https://ift.tt/2u73mX0

Postoperative imatinib in patients with intermediate risk gastrointestinal stromal tumor

Future Oncology, Ahead of Print.


https://ift.tt/2KOR0Kv

SMYD3 promoter hypomethylation is associated with the risk of colorectal cancer

Future Oncology, Ahead of Print.


https://ift.tt/2NsqCaW

Black–White Breast Cancer Incidence Trends: Effects of Ethnicity

Abstract

Recent reports of converging black and white breast cancer incidence rates have gained much attention, potentially foreshadowing a worsening of the black–white breast cancer mortality disparity. However, these incidence rates also reflect the sum of non-Hispanics and Hispanics that may mask important ethnicity-specific trends. We therefore assessed race- and ethnicity-specific breast cancer trends using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 13 Registries Database (1992–2014). Age-period-cohort models projected rates for 2015–2030. Results confirmed merging of age-standardized incidence rates for blacks and whites circa 2012, but not for non-Hispanic black (NHB) and non-Hispanic white (NHW) women. Incidence rates were highest for NHW women (n = 382 290), followed by NHB women (n = 51 074), and then Hispanic white women (n = 48 651). The sample size for Hispanic blacks was too small for analysis (n = 693). Notably, future incidence rates are expected to slowly increase (2015 through 2030) among NHW women (0.24% per year, 95% confidence interval [CI] = 0.17 to 0.32) and slowly decrease for NHB women (–0.14% per year, 95% CI = –0.15 to –0.13). A putative worsening of the black–white mortality disparity, therefore, seems unlikely. Ethnicity matters when assessing race-specific breast cancer incidence rates.

https://ift.tt/2udgOZJ

Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy

Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy

Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy, Published online: 05 July 2018; doi:10.1038/s41416-018-0168-9

Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy

https://ift.tt/2zdz4HS

Are We Going Nuts on Coconut Oil?

Abstract

Purpose of Review

Sales and consumption of coconut oil have been on the raise due to effective marketing strategies. Coconut oil is stated to offer various benefits including weight loss, improvement in immunity, heart health support, and memory enhancement. Also, it is often portrayed as an excellent source of medium chain triglycerides (MCTs). Here, we review the evidence behind the clinical utility of coconut oil consumption.

Recent Findings

Several studies consistently showed consumption of coconut oil increases low-density lipoprotein cholesterol (LDL-C) and thereby could increase adverse cardiovascular health. Even though coconut oil has relatively high MCT concentration, the clinical benefits of commercial MCT oils cannot be generalized to coconut oil.

Summary

Until the long-term effects of coconut oil on cardiovascular health are clearly established, coconut oil should be considered as a saturated fat and its consumption should not exceed the USDA's daily recommendation (less than 10% of total calorie intake).

https://ift.tt/2lV1HjP

Can visual analogue scale be used in radiologic subjective image quality assessment?

Abstract

Background

Assessment of qualitative or subjective image quality in radiology is traditionally performed using a fixed-point scale even though reproducibility has proved challenging.

Objective

Image quality of 3-T coronary magnetic resonance (MR) angiography was evaluated using three scoring methods, hypothesizing that a continuous scoring scale like visual analogue scale would improve the assessment.

Materials and methods

Adolescents corrected for transposition of the great arteries with arterial switch operation, ages 9–15 years (n=12), and healthy, age-matched controls (n=12), were examined with 3-D steady-state free precession magnetic resonance imaging. Image quality of the coronary artery origin was evaluated by using a fixed-point scale (1–4), visual analogue scale of 10 cm and a visual analogue scale with reference points (figurative visual analogue scale). Satisfactory image quality was set to a fixed-point scale 3=visual analogue scale/figurative visual analogue scale 6.6 cm. Statistical analysis was performed using Cohen kappa coefficient and agreement index.

Results

The mean interobserver scores for the fixed-point scale, visual analogue scale and figurative visual analogue scale were, respectively, in the left main stem 2.8, 5.7, 7.0; left anterior descending artery 2.8, 4.7, 6.6; circumflex artery 2.5, 4.5, 6.2, and right coronary artery 3.2, 6.3, 7.7. Scoring with a fixed-point scale gave an intraobserver κ of 0.52–0.77 while interobserver κ was lacking. For visual analogue scale and figurative visual analogue scale, intraobserver agreement indices were, respectively, 0.08–0.58 and 0.43–0.71 and interobserver agreement indices were up to 0.5 and 0.65, respectively.

Conclusion

Qualitative image quality evaluation with coronary 3-D steady-state free precession MR angiography, using a visual analogue scale with reference points, had better reproducibility compared to a fixed-point scale and visual analogue scale. Image quality, being a continuum, may be better determined by this method.

https://ift.tt/2KKqKUv

Unsupervised machine learning of radiomic features for predicting treatment response and overall survival of early stage non-small cell lung cancer patients treated with stereotactic body radiation therapy

To predict treatment response and survival of NSCLC patients receiving stereotactic body radiation therapy (SBRT), we develop an unsupervised machine learning method for stratifying patients and extracting meta-features simultaneously based on imaging data.

https://ift.tt/2z8YoyX

A critically ill patient after a colchicine overdose below the lethal dose: a case report

Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported.

https://ift.tt/2ISVoGg

How can the risk of ovarian retorsion be reduced?

In the current treatment of idiopathic ovarian torsion, the use of oophorectomy has declined in favor of preserving the ovary. This approach brings with it the question of how to reduce the possibility of reto...

https://ift.tt/2KyDHBF

Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy

https://ift.tt/2KAgY8g

Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma

Abstract

Background

HIF-1alpha and CAIX proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well. Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and strong stromal reaction and has a dismal prognosis with the currently available treatment modalities.

Methods

We investigated the expression and prognostic role of HIF-1alpha and CAIX in PDAC series from Northern Finland (n = 69) using immunohistochemistry.

Results

In our PDAC cases, 95 and 85% showed HIF-1alpha and CAIX expression, respectively. Low HIF-1alpha expression correlated with poor prognosis, and multivariate analysis identified weak HIF-1alpha intensity as an independent prognostic factor for PDAC-specific deaths (HR 2.176, 95% CI 1.216–3.893; p = 0.009). There was no correlation between HIF-1alpha and CAIX expression levels, and the latter did not relate with survival.

Conclusions

Our findings are in contrast with previous research by finding an association between low HIF-1alpha and poor prognosis. The biological mechanisms remain speculative, but such an unexpected relation with prognosis and absence of correlation between HIF-1alpha and CAIX suggests that the prognostic association of HIF-1alpha may not directly be linked with hypoxia. Accordingly, the role of HIF-1alpha might be more complex than previously thought and the use of this marker as a hypoxia-related prognostic factor should be addressed with caution.

https://ift.tt/2tSOX1m

Evaluation of a new predictor of heart and left anterior descending artery dose in patients treated with adjuvant radiotherapy to the left breast

Heart-sparing techniques are time and resource intensive, although not all patients require the use of these strategies. This study evaluates the performance of different distance metrics in predicting the nee...

https://ift.tt/2tSv0ba

Awareness and Beliefs About Cervical Cancer, the HPV Vaccine, and Cervical Cancer Screening Among Ghanaian Women with Diverse Education Levels

Abstract

Cervical cancer is the leading cause of cancer death among women in Ghana. Cost-effective tools for the primary and secondary prevention of cervical cancer, such as the Pap test, the HPV DNA test, and the HPV vaccine, are available in hospitals and clinics throughout Ghana. However, participation in cervical cancer prevention behaviors is low among Ghanaian women. Our objective was to determine if there were significant differences in cervical cancer awareness and stigmatizing beliefs about women with cervical cancer between Ghanaian women of different education levels. We surveyed 288 Ghanaian women who were at least 18 years old. Data on the participants' demographic characteristics, awareness of cervical cancer, cervical cancer screening, and the HPV vaccine, beliefs about cervical cancer screening, and stigmatizing beliefs about women with cervical cancer was collected. Chi-square tests for independence and Fisher's exact test of independence were preformed to determine if education level was associated with those factors. Participation in cervical cancer screening and uptake of the HPV vaccine was significantly lower among women with less than a senior high school education. Awareness about cervical cancer, cervical cancer screening, and the HPV vaccine was lower among women with less education. Women with lower levels of education were more likely to agree with the negative statements about cervical cancer screening and stigmatizing beliefs about women with cervical cancer. Cervical cancer education interventions that are tailored for Ghanaian women with different educational levels are needed to increase awareness of and participation in cervical cancer prevention strategies.

https://ift.tt/2u6uoOn

A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC)

Abstract

Background

This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients.

Methods

The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated.

Results

A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = − 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode.

Conclusion

NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

https://ift.tt/2zaleGp

A population-based analysis of urban–rural disparities in advanced pancreatic cancer management and outcomes

Abstract

Given the significant morbidity burden associated with advanced pancreatic cancer (APC), its management is complex and frequently requires multidisciplinary care. Because of potential geographical barriers to healthcare access, we aimed to determine the effect of rurality on management and outcomes of APC patients. Patients diagnosed with APC from 2008 to 2015 and received Gemcitabine (Gem), Gemcitabine plus nab-Paclitaxel (Gem/Nab), or FOLFIRINOX at any 1 of 6 British Columbia cancer centers across the province were reviewed. Using postal codes, the Google Maps Distance Matrix determined the distance from each patient's residence to the closest cancer center. Rural and urban status were defined as patients living ≥ 100 and < 100 km from the closest treatment site, respectively. Univariate and Cox regression analyses were applied to examine whether rurality resulted in variations in management and outcomes. In total, we identified 659 patients: median age 68 years, 54.3% men, and 76.6% metastatic disease. For treatment, 67.7, 9.2, and 23.0% received Gem, Gem/Nab, and FOLFIRINOX, respectively. However, there were no differences in baseline clinical characteristics between rural and urban patients (all p > 0.05). Also, there were no significant variations in treatment patterns. For example, time from diagnosis to oncology appointment and time from appointment to treatment were 31.5 and 29.5 days for rural patients and 28.6 and 40.1 days for urban patients, respectively (all p > 0.05). Use of Gem/Nab (10.1% vs 9.1%) and FOLFIRINOX (21.0% vs 23.5%) were similar regardless of rurality. In multivariate Cox regression, risk of death was similar between rural and urban groups (HR 0.864, 95% CI 0.619–1.206, p = 0.09). Our findings suggest that there is no correlation between rurality and outcomes in APC. The strategic and geographic allocation of cancer care delivery across the province of British Columbia may serve as a model for other jurisdictions that experience disparities in the outcomes of cancers that often require complex multidisciplinary care.

https://ift.tt/2u4h0tV

A Sickening Tale

In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors' commentary follows. A 44-year-old man presented to the…

https://ift.tt/2KNBd1s

Cancers, Vol. 10, Pages 224: Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance

Cancers, Vol. 10, Pages 224: Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance

Cancers doi: 10.3390/cancers10070224

Authors: Zachary Schrank Gagan Chhabra Leo Lin Tsatsral Iderzorig Chike Osude Nabiha Khan Adijan Kuckovic Sanjana Singh Rachel J. Miller Neelu Puri

Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways. Acquired resistance to molecularly targeted therapies presents a major clinical challenge in the treatment of lung cancer. Therefore, to address this clinical challenge and to improve lung cancer patient prognosis, we need to understand the mechanism of acquired resistance to current therapies and develop additional novel therapies. This review concentrates on various lung cancer biomarkers, including EGFR, ALK, and BRAF, as well as their potential mechanisms of drug resistance.

https://ift.tt/2MM5iMg

Identifying patients who may benefit from oxaliplatin-containing perioperative chemo(radio)therapy for rectal cancer

https://ift.tt/2lVupkC

Selecting patients with triple negative breast cancer for platinum-based therapy: we still haven't found what we're looking for

https://ift.tt/2u65Bdj

Solitary fibrous tumor of the liver. Report of three cases of a very rare tumor

Abstract

Introduction

Solitary fibrous tumors (SFT) can originate in any site of the body. Hepatic location is extremely rare.

Presentation

We present three cases corresponding to women of 26, 40 and 78 years old, with the diagnose of a liver tumor, compatible with SFT, discovered on abdominal CT, who were submitted to right, left and atypical hepatectomy, respectively. The first patient has undergone multiple interventions for excision of metastatic lesions, and is stable with trabectedin; the second patient is asymptomatic with no evidence of recurrence; the third patient had recurrence of the disease after 16 months and passed away 32 months after diagnosis.

Conclusion

Hepatic malignant SFT is very rare, although should be consider in the differential diagnosis of a single large hepatic tumor. Definitive diagnosis is based on histopathological and immunohistochemical findings; surgery remains the mainstay of treatment and careful follow-up is advised.

https://ift.tt/2z6VCKA

Cancers, Vol. 10, Pages 223: Measuring Surgery Outcomes of Lung Cancer Patients with Concomitant Pulmonary Fibrosis: A Review of the Literature

Cancers, Vol. 10, Pages 223: Measuring Surgery Outcomes of Lung Cancer Patients with Concomitant Pulmonary Fibrosis: A Review of the Literature

Cancers doi: 10.3390/cancers10070223

Authors: Taichiro Goto

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonias, often progresses to restrictive respiratory disturbance and mortality, typically within 10 years. IPF frequently coexists with lung cancer, and the combination of these two disease entities is far more difficult to treat than either lung cancer or IPF alone. In particular, surgery for lung cancer with IPF in the background increases postoperative morbidity and mortality by exacerbating pre-existing IPF, i.e., acute exacerbation of IPF (AEIPF). Furthermore, the long-term outcome after lung cancer surgery is considerably worsened by the presence of IPF. We present here a comprehensive review of AEIPF and the long-term outcomes after surgery.

https://ift.tt/2u3eVyA

SIL1 functions as an oncogene in glioma by AKT/mTOR signaling pathway

https://ift.tt/2MNEGe0

Angiogenesis and vasculogenic mimicry are inhibited by 8-Br-cAMP through activation of the cAMP/PKA pathway in colorectal cancer

https://ift.tt/2z0Yicy

A prospective study on neoadjuvant chemoradiotherapy plus anti-EGFR monoclonal antibody followed by surgery for locally advanced cervical cancer

https://ift.tt/2MNEsUc

Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer

Abstract

Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺), neutrophils (CD66b⁺) and polymorphonuclear-MDSC (PMN-MDSC; CD66b⁺CD11b⁺CD15⁺CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺ cells. PMN-MDSC% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3–739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0–18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.

https://ift.tt/2KEKoS3

Neoadjuvant chemotherapy for breast cancer—background for the indication of locoregional treatment

Abstract

Neoadjuvant chemotherapy (NACT) has been widely adopted into the multidisciplinary management of breast cancer. The prognostic impact of treatment response has been clearly demonstrated. However, the impact of treatment response on the indication for adjuvant radiotherapy is unclear. This review summarizes important implications of NACT and treatment response on the risk of recurrence and locoregional multidisciplinary management from the standpoint of radiation oncology.

https://ift.tt/2zjHEVR

Intraoperative Tracheal Obstruction Management among Patients with Anterior Mediastinal Masses

Background. Patients suffering from undiagnosed obstruction of the central airways: the trachea and main stem bronchi are at increased risk for perioperative and postoperative complications, especially if general anesthesia is performed. Case Description. This report discusses a 30-year-old asymptomatic Caucasian female who faced recurrent distal airway collapse during mediastinoscopy for biopsy of an anterior mediastinal mass, which led to the inability to extubate her. This case examines the necessity of a thorough preoperative assessment especially in patients with undiagnosed tracheal obstruction and a precise coordination between anesthesiologist and surgeon in being able to perform a safe and smooth anesthesia, in order to avoid life-threatening complications and to reduce further morbidity. Methods. The scope of this case report is restricted to publications in all surgical and anesthesiological specialties among adult patient population. Main search key words were as follows: "tracheal obstruction," "general anesthesia," "mediastinum," and "tumors" Results. The literature supports an increased perioperative risk of airway obstruction with the use of general anesthesia in patients with anterior mediastinal masses. This case report suggests a perioperative anesthetic management modality for patients presenting with anterior mediastinal masses and who are at high risk of cardiovascular compression and tracheal obstruction. Thus, it is highly important to note that evidence-based recommendations are not available in the literature. Conclusions. This case report suggests perioperative management modalities performed by anesthesiologists in order to minimize the risk of airway obstruction among patients having anterior mediastinal masses and shed the lights on the importance of proper anesthetic and surgical planning in order to prevent intraoperative complications and improve the quality of healthcare provided to patients presenting critical cases.

https://ift.tt/2MKT3jg

Quality Assurance in Melanoma Care: The EU-MELACARE study

Publication date: Available online 3 July 2018
Source:European Journal of Surgical Oncology
Author(s): Antonio Sommariva, Ana-Maria Forsea, Domenic Agius, Paolo Antonio Ascierto, Esther Bastiaannet, Lorenzo Borgognoni, Anna Demetriou, Claus Garbe, Zivana Gavric, Marko Hocevar, Kaire Innos, Siri Larønningen, Marieke Louwman, Trude Eid Robsahm, Piotr Rutkwoski, Alexander van Akkooi, Manuel Zorzi, Sandro Pasquali, Cornelis van de Velde, Carlo Riccardo Rossi
BackgroundA significant disparity regarding survival outcome for melanoma among European regions is well recognized and access to high quality care for European melanoma patients needs to be improved. There is an unmet need for the implementation of minimal standard of care within defined clinical pathways and Quality Assurance (QA) indicators.ObjectiveThe EU-MELACARE study aims to identify shared variables for cutaneous melanoma cases recorded in melanoma registries across Europe.Material and methodsOpinion leaders involved in melanoma data registration and care quality analysis in 34 European countries were invited to respond to an expert survey covering questions regarding the melanoma registration practice in their countries and the characteristics, coverage and variables collected by the relevant melanoma registries.ResultsData regarding 13 melanoma registries from 11 European countries contributed to the study. The majority (61,5%) were population based registries and more than half (62%) had national coverage. The included registries collected a median of 38 variables (Interquartile Range, IRQ 21-76). We identified 24 shared variables available in >70% of registries.ConclusionsThis study provides valuable specific information on information recorded for melanoma cases are registered within Europe. A core of shared variables has been identified, which will constitute the basis for a standardized set of QA indicators for assessing and monitoring melanoma care across European countries.



https://ift.tt/2Nq9GSy

Micro-computed tomography (micro-CT) for intraoperative surgical margin assessment of breast cancer: a feasibility study in breast conserving surgery

Publication date: Available online 3 July 2018
Source:European Journal of Surgical Oncology
Author(s): Si-Qi Qiu, Monique D. Dorrius, Steven J. de Jongh, Liesbeth Jansen, Jakob de Vries, Carolien P. Schröder, Guo-Jun Zhang, Elisabeth G.E. de Vries, Bert van der Vegt, Gooitzen M. van Dam
PurposeAround 15%-30% of patients receiving breast-conserving surgery (BCS) for invasive breast carcinoma or ductal carcinoma in situ (DCIS) need a reoperation due to tumor-positive margins at final histopathology. Currently available intraoperative surgical margin assessment modalities all have specific limitations. Therefore, we aimed to assess the feasibility and accuracy of micro-computed tomography (micro-CT) as a novel method for intraoperative margin assessment in BCS.MethodsLumpectomy specimens from 30 consecutive patients diagnosed with invasive breast cancer or DCIS were imaged using a micro-CT. Margin status was assessed on micro-CT images by two investigators who were blinded to the final histopathological margin status. The micro-CT margin status was compared with the histopathological margin status.ResultsThe margin status could be assessed by micro-CT in 29 out of 30 patients. Of these, nine patients had a positive tumor margin and 20 a negative tumor margin at final histopathology. Margin status evaluation by micro-CT took always less than 15 minutes. The margin status in 25 patients was correctly predicted by micro-CT. There were four false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of micro-CT in margin status prediction were 86%, 56%, 100%, 100% and 83%, respectively. With micro-CT, the positive margin rate could potentially have been reduced from 31% to 14%.ConclusionsWhole lumpectomy specimen micro-CT scanning is a promising technique for intraoperative margin assessment in BCS. Intraoperative quick feedback on the margin status could potentially lead to a reduction in the number of reoperations.



https://ift.tt/2IRHYdz

Surgery for metachronous metastasis of soft tissue sarcoma – A magnitude of benefit analysis using propensity score methods

Publication date: Available online 3 July 2018
Source:European Journal of Surgical Oncology
Author(s): Maria A. Smolle, Veroniek M. van Praag, Florian Posch, Marko Bergovec, Lukas Leitner, Jörg Friesenbichler, Ronald Heregger, Jakob M. Riedl, Martin Pichler, Armin Gerger, Joanna Szkandera, Herbert Stöger, Freyja-Maria Smolle-Jüttner, Bernadette Liegl-Atzwanger, Marta Fiocco, Michiel AJ. van de Sande, Andreas Leithner
IntroductionMetastasectomy is hypothesised to improve OS in metastatic STS, but evidence in favour of this approach derives from non-controlled single-arm cohorts affected by selection bias. The objective was to quantify the effect of metastasectomy vs. non-surgical management on overall survival (OS) in patients with metachronous metastases from extremity and trunk soft tissue sarcoma (STS).Materials and MethodsFrom a population of 1578 STS patients, 135 patients who underwent surgery for localised STS at two European centres between 1998 and 2015, developing metachronous STS metastases, were retrospectively included. Propensity score analyses with inverse-probability-of-treatment-weights (IPTW) and landmark analyses were performed to control for selection and immortal time bias, respectively.ResultsOS was significantly longer in the 68 patients undergoing metastasectomy than in the 67 patients who were treated non-invasively for their metastasis (10-year OS: 23% vs. 4%; hazard ratio (HR)=0.34, 95%CI: 0.22-0.53, p<0.0001). This association prevailed after IPTW-weighting of the data to control for the higher prevalence of favourable prognostic factors in the surgery group (adjusted 10-year OS: 17% vs. 3%, log-rank p<0.0001; HR=0.33, 95%CI: 0.20-0.52, p<0.0001). Five-year OS estimates were 27.8% in patients who had and 14.5% in patients who had not undergone metastasectomy within the first 3 months after metastasis diagnosis (p<0.0001).ConclusionIn this observational bi-centre study, metastasectomy was associated with prolonged survival in patients with metachronous STS metastases. In the absence of randomized studies, our results indicate that metastasectomy should be clearly considered as an important treatment option for metachronous STS metastases.



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Acute Pain Is Associated With Chronic Opioid Use After Total Knee Arthroplasty

Background and Objectives Pain scores are routinely reported in clinical practice, and we wanted to examine whether this routinely measured, patient-reported variable provides prognostic information, especially with regard to chronic opioid use, after taking preoperative and perioperative variables into account in a preoperative opioid user population. Methods In 32,874 preoperative opioid users undergoing primary total knee arthroplasty at Veterans Affairs hospitals between 2010 and 2015, we compared preoperative and perioperative characteristics in patients reporting lower versus higher acute pain (scores ≤4/10 vs >4/10 averaged over days 1–3). We calculated the propensity for lower acute pain based on all available data. After 1:1 propensity score matching, to identify similar patients differing only in acute pain, we contrasted rates of chronic significant opioid use (mean >30 mg/d in morphine equivalents) beyond postoperative month 3, discharge prescriptions, and changes in postoperative versus preoperative dose categories. Sensitivity analysis examined associations with dose escalation. Results Rates of chronic significant opioid use (21% overall) differed in patients with lower versus higher acute pain (36% vs 64% of the overall cohort). After propensity matching (total n = 20,926 patients) and adjusting for all significant factors, lower acute pain was associated with less chronic significant opioid use (rates 12% vs 16%), smaller discharge prescriptions (ie, supply

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Discriminating radiation injury from recurrent tumor with [ 18 F]PARPi and amino acid PET in mouse models

Abstract

Background

Radiation injury can be indistinguishable from recurrent tumor on standard imaging. Current protocols for this differential diagnosis require one or more follow-up imaging studies, long dynamic acquisitions, or complex image post-processing; despite much research, the inability to confidently distinguish between these two entities continues to pose a significant dilemma for the treating clinician. Using mouse models of both glioblastoma and radiation necrosis, we tested the potential of poly(ADP-ribose) polymerase (PARP)-targeted PET imaging with [¹⁸F]PARPi to better discriminate radiation injury from tumor.

Results

In mice with experimental radiation necrosis, lesion uptake on [¹⁸F]PARPi-PET was similar to contralateral uptake (1.02 ± 0.26 lesion/contralateral %IA/cc_max ratio), while [¹⁸F]FET-PET clearly delineated the contrast-enhancing region on MR (2.12 ± 0.16 lesion/contralateral %IA/cc_max ratio). In mice with focal intracranial U251 xenografts, tumor visualization on PARPi-PET was superior to FET-PET, and lesion-to-contralateral activity ratios (max/max, p = 0.034) were higher on PARPi-PET than on FET-PET.

Conclusions

A murine model of radiation necrosis does not demonstrate [¹⁸F]PARPi avidity, and [¹⁸F]PARPi-PET is better than [¹⁸F]FET-PET in distinguishing radiation injury from brain tumor. [¹⁸F]PARPi-PET can be used for discrimination between recurrent tumor and radiation injury within a single, static imaging session, which may be of value to resolve a common dilemma in neuro-oncology.

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Macrophagic myofasciitis: a challenging diagnosis

A 25-year-old man admitted for generalised muscle pain with an insidious onset 3 years ago. He had exercise intolerance and decrease in muscle strength, requiring gait support. He was previously healthy, with no chronic medication or recent history of drugs or toxics. National vaccination plan actualised with hepatitis B and tetanus vaccines administered 10 and 2 years, respectively, before symptom onset. No analytical, imaging or electromyography changes were found. Muscle biopsy revealed an inflammatory infiltrate predominantly macrophagic with aluminium deposits suggestive of macrophagic myofasciitis (MMF). It is probably associated with vaccines previously administered. MMF lesion can be regarded as pathological only if detected at least 18 months after last aluminic immunisation, as our case illustrates.

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Rare glomangiosarcoma of the tongue

The glomus tumour is a rare neoplasm derived from the glomus apparatus. Subungual sites are most common with only three published cases involving the dorsal tongue. To our knowledge, this is the first case of an intraoral malignant glomus tumour (glomangiosarcoma) to be published in English literature. We report a case of a single glomus tumour located on the posterior dorsal tongue of a middle-aged man, which was surgically excised. Immunohistological features were indicative of a glomus tumour; however, in this case, malignant features were also discovered, warranting re-excision.

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Apert syndrome: Be aware of the 'dodgy hip!

Apert syndrome is a rare congenital disorder characterised by craniosynostosis, midface hypoplasia and syndactyly of hands and feet. Here we present a case of a 44-year-old woman, with a genetic diagnosis of Apert syndrome from birth, who presented with symptomatic left-sided hip osteoarthritis secondary to femoral abnormalities. She proceeded to have a total hip replacement. This case report describes the rare occurrence to identify a possible association between Apert syndrome and hip abnormalities.

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Clinical spectrum of Dyke-Davidoff-Masson syndrome in the adult: an atypical presentation and review of literature

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare condition usually diagnosed in paediatric patients with clinical features of hemiparesis, seizures, mental retardation and contralateral cerebral hemiatrophy on neuroimaging. This report follows the case of a 22-year-old man presenting with seizures and hemiatrophy and hemiparesis. On review of cases the most common neuroimaging findings were cerebral hemiatrophy (100%) followed by hemicalvarial thickening (71.4%) and hyperpneumatisation of sinuses (71.4%). Apart from our patient, all nine cases with data on epilepsy control had drug-resistant epilepsy. The onset of seizures in adulthood, block vertebra, short stature, absence of mental retardation and well-controlled epilepsy on monotherapy makes our case exceptional—even bringing to mind the possibility of a DDMS variant. This report exhaustively reviews the wide range of clinical and radiological manifestations of DDMS in the adult, thereby adding to the literature on an unusual syndrome that causes significant neurological morbidity.

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Oropharyngeal paraganglioma presenting with stridor: an unusual presentation

Head and neck paraganglioma is a rare disease to encounter in clinical practice and involvement of the base of the tongue in the oropharynx is yet to be described in the current literature. Although various surgical approaches have been described in the literature, transcervical mandibular swing is an effective technique for adequate exposure and complete excision of the oropharyngeal paraganglioma with adequate control on bleeding especially when it is assisted by coblation.

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A garlic burn

Description 

A 45-year-old woman presented with a 12 hour history of painful blisters and erythema over the dorsum of her left great toe. The patient reported applying freshly sliced raw garlic to the dorsum of her left great toe during the past 4 weeks for up to 4 hours a day to treat a fungal nail infection.

On examination, the left great toe was swollen, erythematous and blistering. Her great toenail was yellow and slightly lifted from the nail bed. Clinically, she had a partial thickness burn and onychomycosis (figure 1). The skin on the toe was pH 9. The toe was irrigated with water until a normal pH was reached, and the blisters de-roofed.

Figure 1

Clinical appearance of garlic burn in this patient. The image shows blistering and erythema consistent with a partial thickness burn. The toenail is discoloured due to the underlying fungal...

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