Comparison of efficacy and safety of preoperative Chemoradiotherapy in locally advanced upper and middle/lower rectal cancer

Abstract

Background

We aimed to explore the efficacy and safety profile of preoperative neoadjuvant chemoradiation (NACRT) in locally advanced rectal cancer (LARC) in upper rectum versus middle/lower rectum.

Methods

The study included 173 patients with stage II or III (T2-4b, N0-2b) LARC who underwent NACRT followed by total mesorectal excision (TME) between January 2011 and October 2016. Cox regression, log-rank test, and Kaplan–Meier curves were calculated.

Results

Among the 173 patients, 58 had lesions in the upper rectum and 115 patients had lesions in middle/lower rectum. In a median follow-up of 35 months (range, 6–73 months), the 5-year disease-free survival (DFS) and overall survival (OS) were 84% and 88% for the patients with upper rectal cancer and 77% and 68% for those with middle/lower rectal cancer (P = 0.251 and P = 0.058, respectively). The 5-year DFS (P = 0.012) and OS (P = 0.003) were better in the NACRT responders [tumor regression grade (TRG) 0 or 1] compared with nonresponders (TRG 2 or 3). The independent prognostic factor of favorable response to NACRT was the FOLFOX regimen (P = 0.004).

Conclusions

Patients with LARC in the upper rectum who underwent NACRT followed by TME had similar DFS and a trend toward longer OS, compared with those who had middle/lower rectal lesions. Furthermore, FOLFOX may yield superior results than fluoropyrimidine based regimen during NACRT. NACRT might be an alternative option for patients with LARC in the upper rectum as it has a favorable pathological complete response rate and comparable clinical outcomes when compared with patients with LARC in middle/lower rectum.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pKvux5

Clinical outcome after particle therapy for meningiomas of the skull base: toxicity and local control in patients treated with active rasterscanning

Abstract

Background

Meningiomas of the skull base account for 25–30% of all meningiomas. Due to the complex structure of the cranial base and its close proximity to critical structures, surgery is often associated with substantial morbidity. Treatment options include observation, aggressive surgical intervention, stereotactic or conventional radiotherapy.

In this analysis we evaluate the outcome of 110 patients with meningiomas of the skull base treated with particle therapy. It was performed within the framework of the "clinical research group heavy ion therapy" and supported by the German Research Council (DFG, KFO 214).

Methods

Between May 2010 and November 2014, 110 Patients with skull base meningioma were treated with particle radiotherapy at the Heidelberg Ion Therapy Center (HIT). Primary localizations included the sphenoid wing (n = 42), petroclival region (n = 23), cavernous sinus (n = 4), sella (n = 10) and olfactory nerve (n = 4). Sixty meningiomas were benign (WHO °I); whereas 8 were high-risk (WHO °II (n = 7) and °III (n = 1)). In 42 cases histology was not examined, since no surgery was performed.

Proton (n = 104) or carbon ion (n = 6) radiotherapy was applied at Heidelberg Ion Therapy Center (HIT) using raster-scanning technique for active beam delivery. Fifty one patients (46.4%) received radiotherapy due to tumor progression, 17 (15.5%) after surgical resection and 42 (38.2%) as primary treatment.

Results

Median follow-up in this analysis was 46,8 months (95% CI 39,9–53,7; Q1-Q3 34,3–61,7). Particle radiotherapy could be performed safely without toxicity-related interruptions. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered excellent overall local control rates with 100% progression-free survival (PFS) after 36 months and 96.6% after 60 months. Median PFS was not reached due to the small number of events. Histology significantly impacted PFS with superior PFS after 5 years for low-risk tumors (96.6% vs. 75.0%, p = 0,02). Overall survival was 96.2% after 60 months and 92.0% after 72 months from therapy. Of six documented deaths, five were definitely not and the sixth probably not meningioma-related.

Conclusion

Particle radiotherapy is an excellent treatment option for patients with meningiomas of the skull base and can lead to long-term tumor control with minimal side effects. Other prospective studies with longer follow-up will be necessary to further confirm the role of particle radiotherapy in skull base meningioma.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IWdUiq

Knowledge-based IMRT planning for individual liver cancer patients using a novel specific model

Abstract

Background

The purpose of this work is to benchmark RapidPlan against clinical plans for liver Intensity-modulated radiotherapy (IMRT) treatment of patients with special anatomical characteristics, and to investigate the prediction capability of the general model (Model-G) versus our specific model (Model-S).

Methods

A library consisting of 60 liver cancer patients with IMRT planning was used to set up two models (Model-S, Model-G), using the RapidPlan knowledge-based planning system. Model-S consisted of 30 patients with special anatomical characteristics where the distance from planning target volume (PTV) to the right kidney was less than three centimeters and Model-G was configurated using all 60 patients in this library. Knowledge-based IMRT plans were created for the evaluation group formed of 13 patients similar to those included in Model-S by Model-G, Model-S and manually (M), named RPG-plans, RPS-plans and M-plans, respectively. The differences in the dose-volume histograms (DVHs) were compared, not only between RP-plans and their respective M-plans, but also between RPG-plans and RPS-plans.

Results

For all 13 patients, RapidPlan could automatically produce clinically acceptable plans. Comparing RP-plans to M-plans, RP-plans improved V_95% of PTV and had greater dose sparing in the right kidney. For the normal liver, RPG-plans delivered similar doses, while RPS-plans delivered a higher dose than M-plans. With respect to RapidPlan models, RPS-plans had better conformity index (CI) values and delivered lower doses to the right kidney V_20Gy and maximizing point doses to spinal cord, while delivering higher doses to the normal liver.

Conclusion

The study shows that RapidPlan can create high-quality plans, and our specific model can improve the CI of PTV, resulting in more sparing of OAR in IMRT for individual liver cancer patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pJJozh

The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

Abstract

Background

Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer.

Method

Altogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected.

Result

With a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5–8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS.

Conclusion

TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GdCgSU

To fast, or not to fast before chemotherapy, that is the question

Abstract

Fasting in disease prevention and treatment has recently become a popular topic, particularly in the context of oncology. Unfortunately, the growing attention paid by the media has created a background of speculations and ambiguous messages.

The attitude towards the role of fasting in cancer patients should be very cautious, as the risk of malnutrition/sarcopenia and disinformation may be associated with this approach.

Whether the results obtained by fasting in the cellular and animal models can be transferred to cancer patients is still to be ascertained. At the moment, more preclinical studies are required to determine in which cancers, at which stage, and in what combinations fasting, fasting-mimicking diets or caloric restriction mimetics may prove effective.

So, despite the "rumors" of marketing and media, nowadays fasting and calorie restriction around CT represent only a promising intuition, which requires proper efforts and time to be validated by evidence-based clinical data.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IVo7eZ

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

Abstract

Background

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.

Methods

This retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m² with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1–4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.

Results

Of the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45–1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37–1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98–4.87; p = 0.057).

Conclusions

The results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2ITeFbW

Erlotinib treatment after platinum-based therapy in elderly patients with non-small-cell lung cancer in routine clinical practice – results from the ElderTac study

Abstract

Background

In this prospective non-interventional study, the effectiveness and tolerability of erlotinib in elderly patients with non-small-cell lung cancer (NSCLC) after ≥1 platinum-based chemotherapy were assessed.

Methods

A total of 385 patients ≥65 years of age with advanced NSCLC receiving erlotinib were observed over 12 months. The primary endpoint was the 1-year overall survival (OS) rate.

Results

Patients were predominantly Caucasian (99.2%), a mean of 73 years old; 24.7% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Most common tumor histologies were adenocarcinoma (64.9%) and squamous cell carcinoma (22.3%). Of 119 patients tested, 15.1% had an activating epidermal growth factor receptor gene (EGFR) mutation. The 1-year OS rate was 31% (95% CI 25–36) with a median OS of 7.1 months (95% CI 6.0–7.9). OS was significantly better in females than males (p = 0.0258) and in patients with an EGFR mutation compared to EGFR wild-type patients (p = 0.0004). OS was not affected by age (p = 0.3436) and ECOG PS (p = 0.5364). Patients with squamous NSCLC tended to live longer than patients with non-squamous EGFR wild-type tumors (median OS: 8.6 vs 5.5 months). Cough and dyspnea improved during the observation period. The erlotinib safety profile was comparable to that in previous studies with rash (45.2%) and diarrhea (22.6%) being the most frequently reported adverse events.

Conclusions

Erlotinib represents a suitable palliative treatment option in further therapy lines for elderly patients with advanced NSCLC. The results obtained under real-life conditions add to our understanding of the benefits and risks of erlotinib in routine clinical practice.

Trial registration

BfArM (https://www.bfarm.de; ML23023); ClinicalTrials.gov (NCT01535729; 20 Feb 2012).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GctO6l

Knockdown delta-5-desaturase in breast cancer cells that overexpress COX-2 results in inhibition of growth, migration and invasion via a dihomo-γ-linolenic acid peroxidation dependent mechanism

Abstract

Background

Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional membrane-bound enzyme that typically metabolizes arachidonic acid (downstream ω-6 fatty acid) to form 2-series of prostaglandins known to be involved in cancer development. Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis. Our lab recently demonstrated that COX-2 can also metabolize dihomo-γ-linolenic acid (DGLA, a precursor of ω-6 arachidonic acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that can inhibit growth and migration of colon and pancreatic cancer cells. We thus tested whether our strategy of knocking down delta-5-desaturase (D5D, the key enzyme that converts DGLA to arachidonic acid) in breast cancer cells overexpressing COX-2 can also be used to promote 8-HOA formation, thereby suppressing cancer growth, migration, and invasion.

Methods

SiRNA and shRNA transfection were used to knock down D5D expression in MDA-MB 231 and 4 T1 cells (human and mouse breast cancer cell lines expressing high COX-2, respectively). Colony formation assay, FITC Annexin V/PI double staining, wound healing and transwell assay were used to assess the effect of our strategy on inhibition of cancer growth, migration, and invasion. GC/MS was used to measure endogenous 8-HOA, and western blotting was performed to evaluate the altered key protein expressions upon the treatments.

Results

We demonstrated that D5D knockdown licenses DGLA to inhibit growth of breast cancer cells via promoting formation of 8-HOA that can inhibit histone deacetylase and activate cell apoptotic proteins, such as procaspase 9 and PARP. Our strategy can also significantly inhibit cancer migration and invasion, associated with altered expression of MMP-2/− 9, E-cadherin, vimentin and snail. In addition, D5D knockdown and DGLA supplementation greatly enhanced the efficacy of 5-fluorouracil on breast cancer growth and migration.

Conclusions

Consistent to our previous studies on colon and pancreatic cancer, here we demonstrate again that the high level of COX-2 in breast cancer cells can be capitalized on inhibiting cancer growth and migration. The outcome of this translational research could guide us to develop new anti-cancer strategy and/or to improve current chemotherapy for breast cancer treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IXXeHo

Editorial Board

Publication date: April 2018
Source:Acta Histochemica, Volume 120, Issue 3





from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GuSdaA

Retraction notice to “CD133+/CD44+/Oct4+/Nestin+ stem-like cells isolated from Panc-1 cell line may contribute to multi-resistance and metastasis of pancreatic cancer” [Acta Histochemica 115 (2013) 349–356]

Publication date: April 2018
Source:Acta Histochemica, Volume 120, Issue 3
Author(s): Dongqing Wang, Haitao Zhu, Ying Zhu, Yanfang Liu, Huiling Shen, Ruigen Yin, Zhijian Zhang, Zhaoliang Su




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2I30DTV

FOLFIRI plus panitumumab in the treatment of wild-type KRAS and wild-type NRAS metastatic colorectal cancer

Abstract

Background

The aim of this study was to investigate the efficacy and safety of first-line panitumumab plus folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) in patients with wild-type KRAS and wild-type NRAS metastatic colorectal cancer (mCRC).

Methods

Patients with wild-type KRAS and wild-type NRAS mCRC presenting to the medical oncology department of the Okmeydani Training and Research Hospital in Istanbul, Turkey, between April 2014 and January 2018 were enrolled in this study.

Results

A total of 64 patients (35 males and 29 females) with a median age of 59 (35–81) years old were enrolled. The median follow-up was 18.9 months, and the median progression-free survival was 13 months. The median overall survival (OS) was 26 months in the patients with wild-type KRAS and wild-type NRAS mCRC. It was 90.4% for the 6-month OS, 79.5% for the 1-year OS, 53.7% for the 2-year OS and 31.1% for the 3-year OS. The median OS of the patients who underwent metastasectomies was 40 [95% confidence interval (CI) = 19.9–60.1] months, and the median OS of the patients without metastasectomies was 22 (95% CI = 17.7–26.4) months. There was a statistically significant difference between these (P = 0.007).

Conclusion

The first-line FOLFIRI plus panitumumab was associated with favourable efficacy in the patients with wild-type KRAS and wild-type NRAS mCRC, and it was well tolerated. The removal of the metastases that became resectable after chemotherapy further prolonged the patients' survival.

Trial registration

Retrospectively registered: 33886

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DXty9i

CalliSpheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma: a short-term efficacy and safety study

Abstract

Background

The present study aimed to evaluate the short-term efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres Beads loaded with doxorubicin (DOX) in the treatment of Chinese patients with hepatocellular carcinoma (HCC) compared to conventional TACE (cTACE).

Methods

A total of 54 patients with HCC treated by TACE from June 2016 to February 2017 were retrospectively analyzed. These included 24 cases in the DEB-TACE group and 30 cases in the cTACE group. The clinical efficacy, tumor recurrence rate, and complications were compared between the two groups. Furthermore, liver function tests and alpha-feto protein levels were compared between the two groups before and at 1 week and 1 month after interventional treatment.

Results

There were no significant differences in baseline characteristics (p > 0.05). Tumor response rates and disease control rates in the DEB-TACE group were significantly higher than those in the cTACE group at 3 and 6 months after treatment (p < 0.05). Recurrence rates at 6 months were significantly higher for cTACE compared to DEB-TACE (43.3 vs. 16.7%; p = 0.036). At 1 month, the AFP level in the DEB-TACE group was significantly lower than that in the cTACE group (p = 0.008). At the end of follow-up, four cases in the DEB-TACE group and two cases in the cTACE group were treated with salvage surgery after downstaging the disease. Liver function of both groups improved at 1 month. However, alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in the DEB-TACE group were better than those in the cTACE group (p < 0.05). The incidence of DOX-related complications in the DEB-TACE group was significantly lower than in the cTACE group (p < 0.05).

Conclusion

The short-term efficacy of DEB-TACE is better, and the complication rates are lower compared to cTACE in the treatment of Chinese patients with HCC. However, long-term clinical efficacy and survival benefit should be analyzed in future studies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GsSo6u

Mesh-reinforced pancreaticojejunostomy versus conventional pancreaticojejunostomy after pancreaticoduodenectomy: a retrospective study of 126 patients

Abstract

Background

Pancreatic fistula is a major cause of morbidity and mortality after pancreaticoduodenectomy. The aim of this study is to compare the safety and efficacy of a newly developed technique, namely mesh-reinforced pancreaticojejunostomy, in comparison with the conventional use of pancreaticojejunostomy after undergoing a pancreaticoduodenectomy.

Methods

Data was collected from regarding 126 consecutive patients, who underwent the mesh-reinforced pancreaticojejunostomy or conventional pancreaticojejunostomy, after standard pancreaticoduodenectomy by one group of surgeons, between the time period of 2005 and 2016. This data was collected retrospectively. Surgical parameters and perioperative outcomes were compared between these two groups.

Results

A total of 65 patients received mesh-reinforced pancreaticojejunostomy and 61 underwent conventional pancreaticojejunostomy. There were no substantial differences in surgical parameters, mortality, biliary leakage, delayed gastric emptying, gastrojejunostomy leakage, intra-abdominal fluid collection, postpancreatectomy hemorrhage, reoperation, and the total hospital costs between the two groups. Pancreatic fistula rate (15 versus 34%; p = 0.013), overall surgical morbidity (25 versus 43%; p = 0.032), and length of hospital stay (18 ± 9 versus 23 ± 12 days; p = 0.016) were significantly reduced after mesh-reinforced pancreaticojejunostomy. Multivariate analysis of the postoperative pancreatic fistula revealed that the independent factors that were highly associated with pancreatic fistula were a soft pancreatic texture and the type of conventional pancreaticojejunostomy.

Conclusions

This retrospective single-center study showed that mesh-reinforced pancreaticojejunostomy appears to be a safe technique for pancreaticojejunostomy. It may reduce pancreatic fistula rate and surgical complications after pancreaticoduodenectomy.

Trial registration

This research is waivered from trial registration because it is a retrospective analysis of medical records.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2E1gksw

Treatment of intraoperatively detected peritoneal carcinomatosis of colorectal origin with cytoreductive surgery and intraperitoneal chemotherapy

Abstract

Background

Diagnosis of peritoneal carcinomatosis (PC) may be missed by preoperative imaging. We are presenting our experience with incidentally detected PC of colorectal origin treated with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) at the same operation.

Methods

Between January 2010 and September 2016, 19 patients underwent CRS and IPC due to incidentally detected PC of colorectal origin. Data were analyzed from a prospectively collected database.

Results

The median age was 59 (29–78). In three patients, PC was diagnosed during emergency surgery. The primary tumor was located in the rectum (three patients; one with recurrent disease), left colon (9 patients), and right colon (7 patients). All patients underwent CRS and IPC, and one patient operated laparoscopically. Median peritoneal cancer index (PCI) was 5 (range, 3–14), and complete cytoreduction (CC-0) was achieved in 14 patients. After CRS, 8 patients received early postoperative intraperitoneal chemotherapy (EPIC), 7 patients received hyperthermic intraperitoneal chemotherapy (HIPEC), and 4 patients received both HIPEC and EPIC. The median hospital stay was 9 (6–29) days. Postoperative complications occurred in 6 patients. There was no postoperative mortality. Median follow-up was 40.2 (12–94) months. Five-year overall survival was 63.2%. Estimated mean survival time is longer in patients who underwent complete cytoreduction compared to patients having CC-1 or CC-2 cytoreduction (87.7 vs. 20.3 months; p < 0.001).

Conclusion

Cytoreductive surgery and IPC can be performed safely in patients with intraoperatively detected incidental PC of colorectal origin.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GsS9IC

Thomas L. Slovis (1941-2018)

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2ulMHCF

Matrix metalloproteinase-8 levels in oral samples as a biomarker for periodontitis in the Chinese population: an observational study

Abstract

Background

Clinical evaluation of periodontal inflammation does not fully reflect the disease activity. Extensive studies have been conducted out on gingival crevicular fluid (GCF) components that might serve as potential diagnostic markers for periodontitis, among which matrix metalloproteinase-8 (MMP-8) has shown to be promising, but there were no studies for individuals in China. The aim of this study was to compare clinical diagnostic parameters and levels of active MMP-8 (aMMP-8) in GCF and oral rinse samples from the Chinese patients with varying degrees of periodontal inflammation.

Methods

GCF and oral rinse samples were obtained from 60 participants into two groups, a periodontitis group and a control group, specified by the presence and number of pocket depths or attachment loss. The aMMP-8 levels in GCF and oral rinse samples was quantified by ELISA using specific monoclonal antibodies. Logistic and linear regression models were employed for testing the correlation between aMMP-8 levels and periodontal condition, as well as diagnostic sensitivity and specificity.

Results

Periodontitis group (mean = 24.84 ng/ml) exhibited significantly higher aMMP-8 levels than control group in GCF (p < 0.001). The aMMP-8 levels in oral rinse samples ranged from 0.05 to 2.18 ng/ml, but differences were not statistically significant between the two groups (p > 0.1). Receiver operating characteristic curve analysis showed a highest threshold of 6.66, with a corresponding sensitivity and specificity of 0.8 and 0.9, respectively.

Conclusions

Measuring aMMP-8 levels in GCF may have potentiality for complementary early diagnosis of periodontal disease and inflammation in the Chinese population.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pK05LS

Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines

Abstract

Alzheimer's disease is a neurodegenerative disease that affects 44 million people worldwide, costing the world $605 billion to care for those affected not taking into account the physical and psychological costs for those who care for Alzheimer's patients. Dipentylammonium is a simple amine, which is structurally similar to a number of other identified sigma-1 receptor ligands with high affinities such as (2R-trans)-2butyl-5-heptylpyrrolidine, stearylamine and dodecylamine. This study investigates whether dipentylammonium is able to provide neuroprotective effects similar to those of sigma-1 receptor agonists such as PRE-084. Here we identify dipentylammonium as a sigma-1 receptor ligand with nanomolar affinity. We have found that micromolar concentrations of dipentylammonium protect from glutamate toxicity and prevent NFκB activation in HT-22 cells. Micromolar concentrations of dipentylammonium also protect stably expressing amyloid precursor protein Swedish mutant (APP/Swe) Neuro2A cells from toxicity induced by 150 μM dopamine, suggesting that dipentylammonium may be useful for the treatment of Parkinsonian symptoms in Alzheimer's patients which are often associated with a more rapid deterioration of cognitive and physical ability. Finally, we found that low micromolar concentrations of dipentylammonium could out preform known sigma-1 receptor agonist PRE-084 in potentiating neurite outgrowth in Neuro2A cells, further suggesting that dipentylammonium has a potential use in the treatment of neurodegenerative diseases and could be acting through the sigma-1 receptor.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Gy5Vd4

Anatomical description of the umbilical arteries and impact of their ligation on pelvic and perineal vascular supply after cystectomy in women

Abstract

Objective

In radical cystectomy, the surgeon generally ligates the umbilical artery at its origin. This artery may give rise to several arteries that supply the sexual organs. Our aim was to evaluate pelvic and perineal devascularisation in women after total cystectomy.

Patients and methods

We carried out a prospective anatomical and radiological study. We performed bilateral pelvic dissections of fresh adult female cadavers to identify the dividing branches of the umbilical artery. In parallel, we examined and compared the pre- and postoperative imaging investigations [magnetic resonance imaging (MRI) angiography] in patients undergoing cystectomy for benign disease to quantify the loss of pelvic vascularisation on the postoperative images by identifying the occluded arteries.

Results

The anatomical study together with the radiological study visualised 35 umbilical arteries (n = 70) with their branching patterns and collateral arteries. The uterine artery originated from the umbilical artery in more than 75% of cases (n = 54) of the internal pudendal artery in 34% (n = 24) and the vaginal artery in 43% (n = 30). The postoperative MRI angiograms showed pelvic devascularisation in four patients. Devascularisation was dependent on the level of surgical ligation. In the four patients with loss of pelvic vascular supply, the umbilical artery had been ligated at its origin.

Conclusion

The umbilical artery gives rise to various branches that supply the pelvis and perineum. If the surgeon ligates the umbilical artery at its origin during total cystectomy, there is a significant risk of pelvic and perineal devascularisation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pHPVLP

2017 AACE/Endocrine Society Update on Transgender Medicine

These cases provide key teaching points regarding the endocrine care of transgender patients.
Endocrine Practice

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GyDVGl

Nomograms predict long-term survival for patients with periampullary adenocarcinoma after pancreatoduodenectomy

Abstract

Background

The prognosis of patients with periampullary adenocarcinoma after pancreatoduodenectomy is diverse and not yet clearly illustrated. The aim of this study was to develop a nomogram to predict individual risk of overall survival (OS) and progression-free survival (PFS) in patients with periampullary adenocarcinoma after pancreatoduodenectomy.

Methods

A total of 205 patients with periampullary adenocarcinoma after pancreatoduodenectomy were retrospectively included. OS and PFS were evaluated by the Kaplan-Meier method. Two nomograms for predicting OS and PFS were established, and the predictive accuracy was measured by the concordance index (Cindex) and calibration plots.

Results

Lymph node ratio (LNR), carbohydrate antigen 19–9 (CA19–9) and anatomical location were incorporated into the nomogram for OS prediction and LNR, CA19–9; anatomical location and tumor differentiation were incorporated into the nomogram for PFS prediction. All calibration plots for the probability of OS and PFS fit well. The Cindexes of the nomograms for OS and PFS prediction were 0.678 and 0.68, respectively. The OS and PFS survival times were stratified significantly using the nomogram-predicted survival probabilities.

Conclusions

The present nomograms for OS and PFS prediction can provide valuable information for tailored decision-making for patients with periampullary adenocarcinoma after pancreatoduodenectomy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2uocDgM

Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis

Abstract

Background

Little is known about the prognostic difference of anti-EGFR therapy, cetuximab (CTX) or nimotuzumab (NTZ), concurrently with induction chemotherapy (IC, investigational arm) or RT (control arm) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We conducted this retrospective study to address this.

Methods

We identified 296 patients with newly diagnosed LA-NPC at Sun Yat-Sen University Cancer Center between January 2012 and May 2015. Patients were treated by IC with CCRT or RT and CTX/NTZ was delivered during IC or radiotherapy. Survival outcomes and toxicities between different arms were compared.

Results

In total, there were 149 patients in the investigational arm and 147 in control arm. The 3-year disease-free survival, overall survival, distant metastasis-free survival and locoregional relapse-free survival rates for investigational arm vs. control arm were 84.3% vs. 74.3% (P = 0.027), 94.0% vs. 92.1% (P = 0.673), 88.0% vs. 81.8% (P = 0.147) and 93.3% vs. 88.0% (P = 0.093). Multivariate analysis revealed patients in the control arm achieved significantly worse disease-free survival (HR, 1.497; 95% CI, 1.016–2.206; P = 0.026) compared with those in the investigational arm; however, no significant difference was identified for other endpoints. Patients in the investigational arm experienced more grade 3–4 skin reaction (15.4% vs. 2.0%, P <  0.001) and mucositis (10.1% vs. 3.4%, P = 0.022) during induction phase, but less skin reaction (5.4% vs. 25.9%, P <  0.001) and mucositis (24.8% vs. 36.7%, P = 0.026) during RT.

Conclusions

Our findings suggested that CTX/NTZ concurrently with IC may be a more effective and promising strategy for patients with LA-NPC receiving intensity-modulated radiotherapy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GrqYOr

Mental disorders around cancer diagnosis and increased hospital admission rate - a nationwide cohort study of Swedish cancer patients

Abstract

Background

Whether the emotional distress around cancer diagnosis is associated with the long-term outcomes and care utilization is unknown. We aimed to examine the association of mental disorders around cancer diagnosis with the hospital admission rates of cancer patients thereafter.

Methods

We conducted a nationwide cohort study including 218,508 cancer patients diagnosed in Sweden during 2004–2009 and followed them from 90 days after cancer through 2010. We used a clinical diagnosis of stress-related mental disorders from 90 days before to 90 days after cancer diagnosis as the exposure. We studied first all hospital admissions and then separately three common admissions, including external injuries, infections, and cardiovascular diseases. The Cox model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Four thousand one hundred five patients received a diagnosis of stress-related mental disorders around the cancer diagnosis, and experienced a 35% increased rate of any hospital admission during follow-up (HR: 1.35, 95%CI: 1.28–1.41) as well as hospital admissions for external injuries (HR: 1.89, 95%CI: 1.67–2.14), infections (HR: 1.28, 95%CI: 1.08–1.52), and cardiovascular diseases (HR: 1.16, 95%CI: 1.03–1.30). Similar association was noted for most common cancer types.

Conclusions

These data suggest that cancer patients diagnosed with a stress-related mental disorder immediately before or after cancer diagnosis are subsequently at increased risk of hospital admissions for major comorbidities of cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2uocuKg

Frequency of HPV in oral cavity squamous cell carcinoma

Abstract

Background

The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC.

Methods

Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5⁺/GP6⁺ as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro–Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression.

Results

Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC.

Conclusion

In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GwazYY

GDF15 predict platinum response during first-line chemotherapy and can act as a complementary diagnostic serum biomarker with CA125 in epithelial ovarian cancer

Abstract

Background

Growth differentiation factor 15 (GDF15) has attracted much interest as a novel biomarker for epithelial ovarian carcinoma (EOC). Research focus has been directed at GDF15 as a diagnostic detection, while the prognostic determination of GDF15 in EOC patients remains to be clearly elucidated. The present study aimed to investigate GDF15 level relative to clinicopathological characters, chemoresponse, and clinical outcome of EOC patients.

Methods

Serum from 122 patients with primary diagnosed EOC were analyzed for GDF15 and serum cancer antigen 125 (CA125). All cases were treated with debulking surgery and first-line chemotherapy, and samples were obtained just before debulking surgical treatment and first-line chemotherapy. Subsequently, clinical characteristics, responses to chemotherapy and progression-free survival (PFS) were recorded.

Results

Increasing levels of serum GDF15 was significantly associated with FIGO stage and lymphonodus metastasis. GDF15 and CA125 detection are complementary in the diagnosis of EOC and can be simultaneously profiled. The chemo-resistant EOC patients (median, 1225.0 pg/mL) showed significantly higher GDF15 than chemo-sensitive patients (median, 824.2 pg/mL; P = 0.013). Highly expressed GDF15 was an independent negative prognostic indicator in the PFS (P = 0.026) of the 122 EOC cases in the multivariate analysis. Additionally, patients with high level of serum CA125 significantly associated with suboptimal (P = 0.043) debulking surgery.

Conclusions

Our results provide valuable evidence that GDF15 is related with first-line chemo-resistance, with highly expressed GDF15 being a strong and an independent indicator of shorter PFS in EOC patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2uoBBN6

Depletion of nuclear import protein karyopherin alpha 7 (KPNA7) induces mitotic defects and deformation of nuclei in cancer cells

Abstract

Background

Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the karyopherin alpha nuclear importer family, is expressed at a high level during embryogenesis, reduced to very low or absent levels in most adult tissues but re-expressed in cancer cells.

Methods

We used siRNA-based knock-down of KPNA7 in cancer cell lines, followed by functional assays (proliferation and cell cycle) and immunofluorescent stainings to determine the role of KPNA7 in regulation of cancer cell growth, proper mitosis and nuclear morphology.

Results

In the present study, we show that the silencing of KPNA7 results in a dramatic reduction in pancreatic and breast cancer cell growth, irrespective of the endogenous KPNA7 expression level. This growth inhibition is accompanied by a decrease in the fraction of S-phase cells as well as aberrant number of centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7 depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina proteins, and drastic alterations in nuclear morphology with lobulated and elongated nuclei.

Conclusions

Taken together, our data provide new important evidence on the contribution of KPNA7 to the regulation of cancer cell growth and the maintenance of nuclear envelope environment, and thus deepens our understanding on the impact of nuclear transfer proteins in cancer pathogenesis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GtWM5k

Is double-approach surgery and tenodesis without a gastrocnemius flap better for dealing with proximal fibular osteosarcoma?

Abstract

Background

Resection of proximal fibular osteosarcoma involving the posteromedial aspect of the fibula is challenging. Reconstruction using a gastrocnemius flap may result in significant lateral instability and abnormal knee movement. Furthermore, postoperative gait may be disturbed by foot drop resulting from scarification of the common peroneal nerve.

Methods

Between January 2011 and December 2013, five patients with proximal fibular osteosarcoma were treated via the double-approach procedure using en bloc resection without a gastrocnemius flap. Simultaneously, all patients received one-stage tenodesis of the anterior tibial and toe extensor tendons. Clinical outcomes, including local tumor recurrence, complications, and functional outcomes, were evaluated.

Results

The mean follow-up duration was 47.2 months (range 42–52 months). No patients experienced local recurrence. The patients' Enneking functional scores were excellent (80%) or good (20%) at the final follow-up.

Conclusions

In patients with proximal fibular osteosarcoma, the double-approach procedure allows easier and safer en bloc tumor resection with vessel and nerve protection. One-stage tenodesis without a gastrocnemius flap is associated with good functional outcomes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2um2wsK

Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1 inhibitor PTX008

Abstract

Background

Drug resistance of B-cell precursor acute lymphoblastic leukemia (BP-ALL) cells is conferred by both intrinsic and extrinsic factors, which could be targeted to promote chemo-sensitization. Our previous studies showed that Galectin-3, a lectin that clusters galactose-modified glycoproteins and that has both an intracellular and extracellular location, protects different subtypes of BP-ALL cells against chemotherapy. Galectin-1 is related to Galectin-3 and its expression was previously reported to be restricted to the MLL subtype of BP-ALL.

Methods and results

Here, we report that Galectin-1 is expressed at different levels in and on different subclasses of BP-ALLs. Bone marrow plasma also contains high levels of Galectin-1. PTX008 is an allosteric inhibitor which inhibits Galectin-1 but not Galectin-3-mediated agglutination. The compound reduces migration of BP-ALL cells to CXCL12 and OP9 stromal cells and inhibits fibronectin-mediated adhesion. It also affects cell cycle progression of BCP-ALL cells. PTX008 is cytostatic for BP-ALL cells even when these are co-cultured with protective stroma, and can sensitize ALL cells to vincristine chemotherapy in vitro and in mice.

Conclusions

PTX008 inhibits multiple functions that contribute to BP-ALL survival. The effects of Galectin-1 inhibition on both BP-ALL cell proliferation and migration suggest both the leukemia cells as well as the microenvironment that protects these cells may be targeted.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IV4Gmx

Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DXTRw7

Treatment of hepatocellular carcinoma: a cost analysis of yttrium-90 transarterial radioembolization versus sorafenib

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GcUfgA

Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DXTRw7

Treatment of hepatocellular carcinoma: a cost analysis of yttrium-90 transarterial radioembolization versus sorafenib

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GcUfgA

Fluorescence microscopy of H&E stained cervical biopsies to assist the diagnosis and grading of CIN

Publication date: Available online 26 March 2018
Source:Pathology - Research and Practice
Author(s): Mario R. Castellanos, Vijeyaluxmy Motilal Nehru, Edyta C. Pirog, Lynne Optiz
BackgroundPrevention of cervical cancer is based upon the accurate diagnosis and grading of cervical lesions identified during screening. The pathological classification of cervical intraepithelial neoplasia (CIN) is problematic, as it relies on subjective criteria and is known to have high interobserver variability and low reproducibility. These limitations can result in either over or under treatment of patients. Biomarkers to improve CIN diagnosis have not overcome all these challenges.Main BodyHere we review the use of a promising optical imaging method using eosin-based fluorescence spectroscopy. This technique is able to perform fluorescent analysis of cervical biopsies directly from hematoxylin and eosin (H&E) stained tissues. Eosin is a brominated derivative of fluorescein. Fluorescence characteristics of protein–eosin complexes can demonstrate tissue changes associated with dysplasia and cancer. In this article we review the progress made towards developing eosin-based fluorescence spectroscopy. We describe the various morphologies seen among the CIN grades with this optical method and highlight the progress made to quantitate the spectral image characteristics.ConclusionEosin-based fluorescence spectroscopy can be used to directly examine H&E stained tissue slides. Relevant areas can be imaged and spectral analysis done to obtain objective data to identify and grade cervical lesions.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IQZxf7

Phenotypic and genotypic differences in colorectal carcinoma among Caucasians, Asians, and Hispanics lack statistical significance

Publication date: Available online 26 March 2018
Source:Pathology - Research and Practice
Author(s): Sara J. Hoffman, Mark Li-cheng Wu
Colorectal carcinoma (CRC) has been shown to have both genetics and environmental factors that can promote carcinoma development. Previous studies have found ethnic differences in the distribution of molecular phenotypes of CRC. Very little specific data exist regarding Hispanic CRC, and these data primarily focus on epidemiology or location of carcinoma. Our retrospective study analyzed 562 Caucasian, Asian, and Hispanic CRC patients at the UCI Medical Center from 2004–2012. The results showed that there were no statistically significant differences with respect to mean age, gender or site of carcinoma among the three ethnic groups. There were no statistically significant differences among the three ethnicities with respect to rates of MSI, mutated BRAF, and mutated KRAS. The Caucasian group had a non-significant higher rate of MSI (15%) and BRAF mutation (12%) than the Asian and Hispanic groups. Hispanics had a non-significant higher rate of KRAS mutation (59%) than Caucasians (38%) and Asians (37%). The results of this study demonstrated a higher rate of MSI and BRAF mutation in the Caucasian group and a higher rate of KRAS mutation in the Hispanic group, however differences were not statistically significant.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IVUaeW

Correlations of pri-Let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer after transcatheter arterial chemoembolization

Publication date: Available online 26 March 2018
Source:Pathology - Research and Practice
Author(s): Gang Wang, Cong Bi
Background and aimSingle nucleotide polymorphisms (SNPs) within miRNAs could change their production or affinity with target genes, thus leading to malignant diseases. This study aims to explore correlations of pri-let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer (PLC) after a transcatheter arterial chemoembolization (TACE) surgical procedure.Materials and methodsA total of 302 PLC patients treated with hepatoprotective therapies after TACE were selected to participate in this study and assigned into recurrent and non-recurrent groups. Genotypes of pri-let-7a-1 rs1073997 and pri-let-7a-2 rs629367 were analyzed by Taqman assay. The relationship between PLC with the mutation of each SNP was determined by a multivariate logistic regression analyses. Moreover, the association between survival and pri-let-7 gene polymorphisms was analyzed by the Kaplan-Meier method. The Progress Free Survival (PFS) curve, correlation of pri-let-7a-1 rs629367 with alcohol, HBsAg-positive and TNM III/IV were analyzed by a stratified analysis. Additionally, the risk factors for the recurrence of PLC were analyzed by a multivariate logistic regression analyses.ResultsResults show that the allelic frequency of the pri-let-7a-2 rs629367 SNP in the recurrent group was higher than that of the non-recurrent group. The distribution of CC genotype was significantly higher than non-CC genotype in the recurrent group. Alcohol consumption, positive expression of hepatitis B surface antigen (HBsAg), AC + CC genotype of rs629367 and TNM III/IV were determined to be the risk factors for the recurrence and metastasis of PLC after TACE. We found a positive correlation between pri-let-7a-2 rs629367 with alcohol consumption, HBsAg-positive and TNM III/IV. The median PFS of HBsAg-positive and TNM III/IV patients with the AC + CC genotype of rs629367 was shorter than those with non-AC + CC genotype.ConclusionOur findings provide evidence that patients with PLC that carry the AC + CC genotype of pri-let-7a-2 rs629367 after TACE have a worse prognosis than those who carry the AA genotype. We speculate that the pri-let-7 rs629367 SNP could be used as a predictor of recurrence and metastasis after TACE for patients with PLC.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2upMCxE

Current trends in the surgical management of blister aneurysms. An illustrative case series

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Themistoklis I. Papasilekas, Konstantinos M. Themistoklis, Alexandros A. Andreou
Blister aneurysms are rare lesions characterized by a bleb-like appearance in combination with prominent fragility. They mainly affect the supraclinoid internal carotid artery and they are often thought of as dissecting or even false lesions. Treatment of such lesions has been a matter of debate during the past few years with authors competing, in an ever changing field, for best results. Both surgical and endovascular modalities have been tried, with every technique having though its own limitations and pitfalls. Our article presents a small series of five blister cases, all treated by surgical means (clipping). We also review the relevant literature presenting a brief overview of available surgical options.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2unYn7K

Effect of fluoxetine on three-year recurrence in acute ischemic stroke: A randomized controlled clinical study

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Yitao He, Zhili Cai, Siling Zeng, Siyan Chen, Bingshan Tang, Yubing Liang, Xin Chang, Yi Guo
ObjectiveTo evaluate the effect of fluoxetine on three-year recurrence rate of acute ischemic stroke.Patients and Methods404 enrolled patients with acute ischemic stroke were randomly divided into control and treatment groups, and underwent conventional secondary preventive therapy for ischemic stroke. In addition, the treatment group was administered fluoxetine (20 mg daily for 90 days). A three-year follow-up was performed, and indicators related to risk factors of stroke were assessed at day 90 of follow-up. The effect of fluoxetine on the three-year recurrence rate of acute ischemic stroke was evaluated by survival analysis, as well as multifactor Cox regression analysis.ResultsThe values of systolic blood pressure, blood total cholesterol, blood low density lipoprotein and glycosylated hemoglobin at day 90 of follow-up were significantly lower in treatment group than control group (P = 0.002, P = 0.002, P = 0.018, P = 0.011, respectively). The occurrence rates of epilepsy, gastrointestinal bleeding, syncope, allergic reactions, hemorrhagic infarction, and death were not significantly different between the two groups during the follow-up (P > 0.05). The recurrence-free survival rate of ischemic stroke was significantly lower in the treatment group than control group as assessed by the Kaplan-Meier test (85.1% Vs 75.7%, P = 0.016), as well as the recurrence-free survival rate after day 90 in the three-year follow-up (87.0% Vs 79.3%, P = 0.043). Multifactor Cox regression analysis demonstrated treatment with fluoxetine was an independent factor reducing three-year recurrence in acute ischemic stroke (HR = 0.594, 95% CI: 0.376–0.938).ConclusionTreatment with fluoxetine for 90 days after acute ischemic stroke significantly reduces the three-year recurrence rate of ischemic stroke.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pHnSMC

Effects of white matter lesions on brain perfusion in patients with mild cognitive impairment

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Masato Ishibashi, Noriyuki Kimura, Yasuhiro Aso, Etsuro Matsubara
ObjectiveTo evaluate the effects of white matter lesions on regional cerebral blood flow in subjects with amnestic mild cognitive impairment.Patients and MethodsSeventy-five subjects with mild cognitive impairment (36 men and 39 women; mean age, 78.1 years) were included in the study. We used the Mini-Mental State Examination to assess cognitive function. All subjects underwent brain magnetic resonance imaging and ^99mTc ethylcysteinate dimer single photon emission computed tomography. Subjects were stratified based on the presence or absence of white matter lesions on magnetic resonance imaging. Statistical parametric mapping of differences in regional cerebral blood flow between the two groups were assessed by voxel-by-voxel group analysis using SPM8.ResultsOf all 75 subjects with mild cognitive impairment, 46 (61.3%) had mild to moderate white matter lesions. The prevalence of hypertension tended to be higher in subjects with white matter lesions than in those without white matter lesions. Mini-Mental State Examination scores were significantly lower in subjects with white matter lesions than in those without white matter lesions. Subjects with white matter lesions had decreased regional cerebral blood flow mainly in the frontal, parietal, and medial temporal lobes, as well as the putamen, compared to those without white matter lesions.ConclusionIn subjects with mild cognitive impairment, white matter lesions were associated with cognitive impairment and mainly frontal lobe brain function.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2unYmAI

Long-term effectiveness and safety of stereotactic gamma knife surgery as a primary sole treatment in the management of glomus jagulare tumor

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Raef F.A. Hafez, Magad S. Morgan, Osama M. Fahmy, Hamdy T. Hassan
ObjectiveThis study aims to report and confirm long-term effectiveness and safety of stereotactic Gamma Knife Surgery as a primary sole treatment in the management of 40 glomus jagulare tumors patients.Patients and methodsRetrospective analysis of clinical and radiological outcomes of 40 GJTs consecutive patients treated with GKS as primary sole treatment at International Medical Center (IMC), Cairo-Egypt from the beginning of 2005 till the end of 2014,with mean follow-up period of 84 months (range 36–156 months), mean tumor volume was 6.5 cc, and mean peripheral radiation dose of 15 Gy, to mean isodose curve of 38%.ResultsThe most common neurological deficit at initial evaluation was bulbar symptoms in 24 patients, followed by pulsatile tinnitus in 22, deterioration of hearing in 20 patients. The overall clinical control achieved in 92.5% of patients, while actuarial tumor size control rate post- GKS was 97.5% at 3 years, 97% at 5 years and 92% at 10 years of follow-up period.ConclusionsGamma knife surgery could be used effectively and safely as a primary sole treatment tool in the management of glomus jugulare tumors.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pHw7rR

Segmental neurofibromatosis type 1 complicated with multiple intracranial arteriovenous fistulas: A case study

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Dian He, Yuan Li, Yunli Yu, Gang Cai, Fu Ouyang, Yuchan Lin, Hongjuan Lu, Lan Chu
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder that primarily affects the skin and the nervous system. This condition is called segmental NF1 (also called neurofibromatosis type V) when clinical features are limited to one area of the body. Segmental NF1 is generally thought to result from somatic mosaicism due to a postzygotic mutation in the NF1 gene, thus a test for NF1 gene abnormalities in peripheral blood is usually negative. Here we report a 31-year-old male presenting with epileptic seizures, who had a history of neurofibromas confirmed by biopsy, but lacked a family history of neurofibromatosis. Multiple signs highly suggestive of NF1 and cerebrovascular abnormities were seen, including distended scalp vessels, gingival hyperplasia, cutaneous masses, skin nodules, and café-au-lait macules. Cerebral computed tomography angiography and venography revealed multiple intracranial arteriovenous fistula. However, NF1 genetic testing of peripheral blood failed to detect mutations, deletions or rearrangements in any of the coding exons or neighboring splice sites. A diagnosis of segmental NF1 was still warranted. To the best of our knowledge, this is the first case study of segmental NF1 complicated with multiple intracranial arteriovenous fistulas.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2ujHN97

Marked effectiveness of low-dose oral methotrexate for steroid-resistant idiopathic hypertrophic pachymeningitis: Case report

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Hiroki Uchida, Yoshikazu Ogawa, Teiji Tominaga
Idiopathic hypertrophic pachymeningitis (HP) is a rare clinical entity characterized by thickening of the dura mater without obvious underlying disease. High-dose steroid therapy is considered to be the first line for idiopathic HP, but half of patients show resistance for steroid therapy and suffer progressive clinical course. We describe low-dose methotrexate (MTX) administration for recurrent and steroid-resistant idiopathic HP resulting in noticeable improvement without severe adverse effects. A 51-year-old Japanese woman with dermatomyositis first presented with right retro-orbital pain caused by dural thickening in the sella and upper clivus involving the right trigeminal nerve, which was diagnosed as idiopathic HP by transsphenoidal biopsy. High-dose methylprednisolone therapy led to remission, and she remained healthy with low-dose dexamethasone. Three years after the initial therapy she presented with right facial nerve and lower cranial nerve palsies caused by diffuse and significant dural thickening in the posterior cranial fossa. Second highdose methylprednisolone therapy was introduced, but the effect was transient and she suffered aspiration pneumonia. Low-dose oral MTX therapy was begun, and her symptoms were almost resolved and dural thickening was remarkably improved without severe adverse effects. Lowdose MTX may be a more appropriate choice for idiopathic HP than steroid administration. Randomized controlled clinical trials are now needed.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2uugycb

Novel XK mutation in a McLeod patient diagnosed after heart transplant

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Chloé Laurencin, Laurent Sebbag, Guillemette Jousserand, Marie Demontes, Lia Campean, Francoise Thivolet-Bejui, Anne Sophie Lebre, Stephane Thobois




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pHw5QL

Epidemiology and short-term surgical outcomes of children presenting with cerebellar tumors

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): Balagangadhar R. Totapally, Ashish H. Shah, Toba Niazi
ObjectivePosterior fossa tumor surgery in children poses a significant morbidity and mortality. Large multi-institutional datasets characterizing the epidemiology and morbidity of children undergoing posterior fossa tumor surgery are lacking. The objective of this study is to describe the epidemiology and short term surgical outcomes of children presenting with cerebellar tumors.Patients and methodsA retrospective review of the Kids Inpatient Database (KID) for all hospital discharges in 2012 with a diagnosis of cerebellar tumor (ICD-9 diagnosis code 191.6) was performed and filtered with the ICD-9 procedure code 01.59 (other excision or destruction of lesion or tissue of brain). All children in this cohort were compared with all other children discharged without cerebellar tumors recorded in the database.ResultsA total of 461 (1.7/10,000 discharges) children with a diagnosis of cerebellar tumor who had surgical resection of their tumor were discharged during 2012. Compared with the control group, children undergoing cerebellar tumor excision had an increased length of hospital stay (8 vs. 2 days, p < 0.001), discharge to skilled nursing home facilities/home health care (12% vs. 4.6%, p < 0.001), increased hospital charges ($125,747 vs. $14,018, p < 0.001), and mortality (0.87% vs. 0.3%, p = 0.028). Hydrocephalus was treated via external ventriculostomy (EVD) (31%, n = 143) and/or shunt (17%, n = 78), and patients who required an EVD were more likely to receive a shunt (56% vs. 26%, p < 0.001). Mechanical ventilation (7.8%) and ultimately tracheostomy (1.5%) was necessary in few children following cerebellar tumor excision.ConclusionsAs expected, surgical treatment of cerebellar tumors in children may pose significant morbidity. Our exploratory study identifies these patients as a potential high-risk cohort in the United States that may require intensive airway management, treatment of hydrocephalus and long-term nursing support.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pHw4wb

Editorial Board/Aims & Scope

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2G9UQ2z

Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a potential role of macrophages

Abstract

Background

We sought to identify the carcinoembryonic antigen (CEA) as a marker of radioresistance in rectal cancer.

Methods

From July 1997 to January 2008, 104 patients with stage II or III rectal cancer who were treated with post-operative radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the actuarial rates of overall survival (OS), distant metastasis (DM), and local recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. We used THP-1 monocyte cell lines for macrophage differentiation (M0, M1 or M2). The RNA extracted from the macrophages was analyzed via a genomic method in the core laboratory. The radiosensitivities of CEA-rich LS1034 cells were compared between cells with and without the conditioned media from CEA-stimulated macrophages.

Results

Preoperative CEA levels ≥10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p = 0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA levels < 10 ng/mL and ≥10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively. The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA elicited a dose-response relationship with M2 differentiation. In the CEA-stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells elicited an increase in the numbers of LS180, SW620, and LS1034 cells after irradiation. CEA caused the M2 differentiation of the macrophages.

Conclusion

Pretreatment CEA levels ≥10 ng/mL are a significant risk factor for OS, DM, and LR following PORT for rectal cancer. CEA causes radioresistance in the presence of M2 macrophages. More comprehensive examinations prior to surgery and intensive adjuvant therapy are suggested for patients with CEA levels ≥10 ng/mL. Further studies of these mechanisms are needed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2unOiHR

Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: Analysis of therapeutic results in 118 cases

The tongue is the most common site of oral cavity cancer, the incidence of which has been found to be rapidly increasing. Patients with squamous cell carcinoma (SCC) of the tongue have a significantly worse prognosis than patients with other oral cavity and other head and neck cancers, because of the high rates of local recurrence following definitive treatment [1]. Early stage tongue SCC is treated by glossectomy or definitive radiotherapy including interstitial brachytherapy. For patients with locally advanced oral SCC, including tongue SCC, primary surgery is widely accepted as the standard treatment, and adjuvant concurrent chemoradiotherapy (CRT) is of benefit in patients with nodal disease [2,3].

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2I8t17f

Upfront surgery versus definitive chemoradiotherapy in patients with human Papillomavirus-associated oropharyngeal squamous cell cancer

Human papillomavirus-associated oropharyngeal squamous cell cancer (HPV-A OPC) incidence has increased significantly over the past two decades, accounting for over 70% of newly diagnosed OPC and now having an incidence higher than that of uterine cervical cancer [1,2]. HPV-A and HPV-negative OPCs are now considered distinct diseases, as evidenced by different etiologies, natural histories [3,4], biomolecular signatures [5–7], treatment responsiveness [8], and staging systems [9]. Numerous prospective trials have demonstrated that HPV positivity confers improved prognosis compared to patients with similar stage HPV-negative tumors [8,10–17].

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2G9UKIf

Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway

We have shown that in HNSCC tumors high expression of PIK3CA is a poor prognosis factor. Increased gene expression leads to augmented level of the p110α protein. This correlates with a decrease in the phosphorylation of the YAP transcription regulator (YAP-P) enabling its translocation to the nucleus and the transcription of YAP-target genes that promote different processes involved in tumorigenesis. The connection between increased PIK3CA expression and YAP nuclear translocation has not been established yet at the molecular level (dotted red arrow).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2I2BNDF

Abstracts from the Joint Meeting of the International Society for NeuroVirology (ISNV) and the Society on NeuroImmune Pharmacology (SNIP) April 10-14, 2018, Chicago, Illinois, USA

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2un5sW1

Knockdown of IFI27 inhibits cell proliferation and invasion in oral squamous cell carcinoma

Abstract

Background

The development of oral squamous cell carcinoma (OSCC) involves genetic mutations, epigenetic gene expression modification, and other processes. It has been reported that IFI27 is upregulated in OSCC, but its function is unknown. The aim of this study was to investigate the role of IFI27 on OSCC cell proliferation and invasion.

Methods

The protein level of IFI27 in OSCC tissues and adjacent tissues was detected by immunohistochemistry. In the OSCC cell model, we designed the IFI27 siRNA to downregulate the expression of IFI27; gene and protein of IFI27 in those models were then detected by Q-PCR and Western blot. MTT assay was used to detect the effect of -IFI27 knockdown on cell proliferation; Annexin V-PI staining flow cytometry was used to detect the effect of IFI27 downregulation on apoptosis of cancer cells. The effect of IFI27 downregulation on oral cancer cell invasion was detected using Transwell assay.

Results

IFI27 was highly expressed in OSCC tissues by immunohistochemical assay. In the OSCC cell model, IFI27 siRNA could downregulate the mRNA and protein expression level of IFI27. As showed in MTT assay, Annexin V-PI assay, and Transwell assay, through the downregulation of IFI27, TSCCA and TCA8113 cell proliferation were inhibited, OSCC cell apoptosis was promoted, and its migration and invasion were inhibited.

Conclusion

IFI27 is involved in the development and progression of OSCC. Its high expression promotes cell proliferation and invasion and reduces apoptosis. These findings may provide new biomarkers and therapeutic targets for OSCC diagnosis and clinical treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2I8cBM1

Biomarker discovery from we to me: Is learning from each patient a new approach?

The immune response is a dynamic multistep process, with a complex system regulation. Identification of predictive biomarkers is therefore challenging. Deep investigation of an exceptional responder to pembrolizumab in ovarian cancer identifies new mechanism of response and highlights the power of individualized medicine strategy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2uoekec

Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer

Background: Tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC. Methods: Data on treatments and diagnostic tests from electronic medical records of two healthcare systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM and OM. For a subgroup with TILs data available, we explored the relationship between TILs and peripheral lymphocyte counts. Results: 1,463 Stage I-III TNBC patients were diagnosed from 2000-2014; 1113 (76%) received neoadjuvant/adjuvant chemotherapy within one year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.16-0.35) and BCM (HR: 0.19, CI: 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (N=70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Conclusion: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IVoDtx

Data Analysis Strategies in Medical Imaging

Radiographic imaging continues to be one of the most effective and clinically useful tools within oncology. Sophistication of artificial intelligence (AI) has allowed for detailed quantification of radiographic characteristics of tissues using predefined engineered algorithms or deep learning methods. Precedents in radiology as well as a wealth of research studies hint at the clinical relevance of these characteristics. However, there are critical challenges associated with the analysis of medical imaging data. While some of these challenges are specific to the imaging field, many others like reproducibility and batch effects are generic and have already been addressed in other quantitative fields such as genomics. Here, we identify these pitfalls and provide recommendations for analysis strategies of medical imaging data including data normalization, development of robust models, and rigorous statistical analyses. Adhering to these recommendations will not only improve analysis quality, but will also enhance precision medicine by allowing better integration of imaging data with other biomedical data sources.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2uisQUU

The long neglected player: modeling tumor uptake to guide optimal dosing

Pharmacokinetic modeling is widely used to support decision making in translational medicine and patient care, traditionally using circulating drug exposure. The development of mechanistic computational models that integrate drug concentrations at the site of action making use of existing knowledge opens a new paradigm in optimal dosing.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IVo82D

ER+ breast cancers resistant to prolonged neoadjuvant letrozole exhibit an E2F4 transcriptional program sensitive to CDK4/6 inhibitors

Purpose:This study aimed to identify biomarkers of resistance to endocrine therapy in ER+ breast cancers (BC) treated with prolonged neoadjuvant letrozole. Experimental Design: We performed targeted DNA and RNA-sequencing in 68 ER+ BC from patients treated with preoperative letrozole (median 7 months). Results:Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC>1, FDR<0.03) in letrozole-resistant tumors with transcription binding data showed significant overlap with 20 E2F4-regulated genes (p=2.56E-15). In patients treated with the CDK4/6 inhibitor palbociclib before surgery, treatment significantly decreased expression of 24 of the 47 most upregulated genes in letrozole-resistant tumors, including 18 of the 20 E2F4 target genes. In long term estrogen-deprived ER+ BC cells, palbociclib also downregulated all 20 E2F4-target genes and P-RB levels, whereas the ER downregulator fulvestrant or paclitaxel only partially suppressed expression of this set of genes and had no effect on P-RB. Finally, an E2F4 activation signature was strongly associated with resistance to aromatase inhibitors in the ACOSOG Z1031B neoadjuvant trial and with an increased risk of relapse in adjuvant treated ER+ tumors in METABRIC. Conclusions: In tumors resistant to prolonged neoadjuvant letrozole, we identified a gene expression signature of E2F4 target activation. CDK4/6 inhibition suppressed E2F4 target gene expression in estrogen-deprived ER+ BC cells and in patients' ER+ tumors, suggesting a potential benefit of adjuvant CDK4/6 inhibitors in patients with ER+ breast cancer who fail to respond to preoperative estrogen deprivation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2umvd99

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants, Published online: 27 March 2018; doi:10.1038/s41416-018-0063-4

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2ukiiVh

MiR-144 suppresses proliferation, invasion, and migration of breast cancer cells through inhibiting CEP55

.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Gdd4vO

Effects of miR-144 on the sensitivity of human anaplastic thyroid carcinoma cells to cisplatin by autophagy regulation

.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GrsAaZ

Rapid exhaustion of auditory neural conduction in a prototypical mitochondrial disease, Friedreich ataxia

The importance of neural processing of temporal cues by the auditory system has been stressed by the discovery of auditory neuropathy spectrum disorders (ANSD) (Starr et al., 1996; Rance and Starr, 2015), in which disrupted auditory-nerve conduction leads to a characteristic pattern of hearing disorder. One striking complaint of ANSD patients is the presence of impaired speech understanding out of proportion with what the auditory sensitivity would predict, particularly in the presence of noise (Kraus et al., 2000; Zeng and Liu, 2006).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Gw820Y

Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees

Following a limb amputation and consequent truncation of nerves, some of the nerve fibers originally directed to the lost part of the body suffer from retrograde Wallerian degeneration. However, a significant part of them survive in the residual portion of the nerve (Navarro et al., 2007). Due to the development of neural interfaces for the peripheral nervous system, i.e. intraneural multichannel electrodes (Navarro et al., 2005), it was recently demonstrated that it is possible to induct meaningful sensations (Dhillon et al., 2005) in the phantom hand of amputees by stimulating the surviving fibers through these interfaces.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2unM23q

Relationships among perceived functional capacity, self-efficacy, and disability after dysvascular amputation

Prosthesis rehabilitation after dysvascular transtibial amputation (TTA) is focused on optimizing functional capacity with limited emphasis on promoting health self-efficacy. Self-efficacy interventions decrease disability for people living with chronic disease, but the influence of self-efficacy on disability is unknown for people with dysvascular TTA.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2ulwsW1

Unilateral necrosis of the tongue caused by embolisation of cholesterol crystals

Cholesterol crystals embolise when an aortic atherosclerotic lesion ruptures and cholesterol crystals are scattered and obstruct small peripheral arterioles. Risk factors include both iatrogenic factors such as intravascular catheterisation, and spontaneous factors for atherosclerosis such as aging, hypertension, dyslipidaemia, and smoking. We describe the case of an 83-year-old Japanese man who developed unilateral, superficial necrosis of the tongue as a result of spontaneous embolisation of cholesterol crystals.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GtfNEJ

Socioeconomic determinants as risk factors for squamous cell carcinoma of the head and neck: a case-control study in Iran

Our aim was to assess the association between different components of sociodemographic status and the risk of developing squamous cell carcinoma (SCC) of the head and neck after we had adjusted for the influence of the known behavioural risk factors of smoking and drinking alcohol. We selected 146 patients with histopathologically-confirmed SCC of the head and neck, and matched them for age and sex with 266 healthy controls for this case-control study. Personal details, occupation, socioeconomic status, smoking, and alcohol consumption were recorded.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DXORYm

Multidetector CT Imaging of Bowel and Mesenteric Injury: Review of Key Signs

In contemporary practice, multidetector computed tomography (MDCT) plays a critical role in the diagnostic evaluation of patients with suspected acute mesenteric and bowel trauma. Although less common than solid organ injuries, it may be seen in up to 5% of blunt trauma patients. Evaluation with CT remains challenging even with improvements in technology. The major imaging signs of mesenteric and bowel trauma and what is known about their applicability in clinical practice are reviewed here. Examples illustrate both the subtlety and variable significance of many of the key signs as well as how these are typically integrated into clinical practice.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Gf1H6P

Pediatric Elbow Injuries

Elbow trauma in children is one of the most commonly encountered musculoskeletal injuries in pediatric radiology. However, elbow injuries in children can be misdiagnosed due to secondary ossification centers unique to pediatric patients. Familiarity of the normal elbow anatomy in children is crucial for an accurate diagnosis. This article seeks to improve diagnostic accuracy of these elbow injuries by reviewing the secondary ossification centers in the elbow in the pediatric population, followed by a discussion of commonly encountered acute and chronic fractures and dislocations.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GsbOsa

Pancreaticobiliary Trauma – A Multimodality Imaging Update

Pancreaticobiliary injury is an uncommon entity which more often occurs in the setting of blunt than penetrating trauma. We present cases of pancreaticobiliary traumatic injuries from our level one trauma center to illustrate an imaging update on the spectrum of injuries and correlation with current grading systems.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2pL6w0n

Imaging and Management of Thoracic Trauma

Thoracic injury results from penetrating and blunt trauma and is a major contributor to overall trauma morbidity and mortality in the United States. Modern imaging algorithms utilize ultrasound, CXR, and CT with intravenous contrast to accurately diagnose and effectively treat patients with acute thoracic trauma. This review focuses on the etiologies, signs and symptoms, imaging, and management of several life-threatening thoracic injuries including tracheobronchial rupture, pulmonary parenchymal injury, hemothorax, pneumothorax, diaphragmatic rupture, and axial skeleton injury.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GsbycG

Cochlear implant function in a patient with Jervell and Lange-Nielsen syndrome after defibrillation by countershock

Jervell and Lange-Nielsen syndrome (JLNS), a rare autosomal recessive congenital QT prolongation syndrome, is characterized by cardiac arrhythmias, syncopal episodes, and profound deafness. A cochlear implant (CI) for patients with JLNS is expected to result in hearing improvement. Sometimes, defibrillation is required if a patient experiences lethal arrhythmia. In this paper, we report a pediatric patient with JLNS who received defibrillation after CI surgery in his right ear at the age of 2 years.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2I5i0n8

Barriers to medication adherence in asthma: the importance of culture and context

Significant disparities exist in asthma outcomes. Racial and ethnic minorities have lower controller medication adherence, which may contribute to differences in asthma morbidity between minority and non-minority groups. The objective of this review is to identify individual, patient-provider communication, and systems issues that contribute to this pattern of medication underuse and to discuss potential strategies for intervention.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2utWIOf

Occupational exposure and asthma

Key Messages – 18-02-0119

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GxmvK6

History of plastic surgery: art, philosophy, and rhinoplasty

The two-hundredth anniversary of K. F. Graefe's "Rhinoplasty", E. Zeis' naming of the specialty of plastic surgery in 1838, and the continuing discussion on what is plastic surgery have prompted this historical-conceptual review with an analytic semantic insight into the meaning of the word "plastic". A literature search has revealed that this term has a dual content composed of an artistic and a philosophic aspect. Progressive development of these two connotations can be traced from their birth in the ceramics and myths of the ancient Greece to their metamorphoses in the fine arts, science, and plasticity philosophy of our days.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GeiNSe

High Abnormal Rate in the Repetitive Nerve Stimulation Test in Acute Onset Myasthenia Gravis

Liik and Punga (2016) reported > 10% decremental response in the repetitive nerve stimulation (RNS) in 1 of 9 patients in the acute onset (AO) group (duration < 4 weeks) of generalized myasthenia gravis (MG). This finding is rather unexpected and contradictory to our common experience of a high rate of abnormal RNS findings in AO MG patients. Because this issue has not been adequately addressed in the literature, we are reporting our findings on this issue.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GgVcjW

Relationship between age and nerve dimensions in Charcot-Marie-Tooth disease. Do we know the reality?

We have read with attention and interest the manuscript by Fabrizi and colleagues, entitled "The spectrum of Charcot-Marie-Tooth disease due to myelin protein zero: An electrodiagnostic, nerve ultrasound and histological study" (Fabrizi et al., 2018). The authors explored, in a wide way, the characteristics of patients affected by myelin protein zero (MPZ)-related Charcot-Marie-Tooth (CMT) disease. They assessed the patients considering clinical examination, nerve conduction study, ultrasound and, in a patient subgroup, biopsy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2G9BwCz

Reply to “High Abnormal Rate in the Repetitive Nerve Stimulation Test in Acute Onset Myasthenia Gravis”

The Letter to the Editor by Lee and Oh in the current issue of Clinical Neurophysiology shows that the decrement was abnormal in the majority of cases with acute onset (AO) myasthenia gravis (MG), derived from the MG database in Alabama between 1987-2014 (Lee and Oh, 2018). This is in contrast to our previous study (Liik and Punga, 2016), which demonstrated a low prevalence of decrement in AO MG patients (< 4 weeks from symptom onset).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DXLosS

Free-Flap Lower Extremity Reconstruction: A Cohort Study and Meta-Analysis of Flap Anastomotic Outcomes between Perforator and Nonperforator Flaps

J reconstr Microsurg
DOI: 10.1055/s-0038-1636939

Introduction Free-flap outcomes in lower extremity reconstruction carry the lowest anastomotic success rates compared with other anatomical sites. Despite their advantages over traditional nonperforator flaps, free perforator flaps have only recently become established in this area due to the additional challenges faced. It is therefore crucial to assess the anastomotic outcomes of perforator and nonperforator free flaps. Methods We performed a single-center retrospective cohort study and combined this with a meta-analysis of the relevant literature. We evaluated three flap anastomotic outcomes: reexploration, operative salvage, and flap failure rates. Results Between January 2010 and June 2015, our center managed 161 patients who underwent lower extremity free-flap reconstruction, which included 76 perforator flaps and 85 nonperforator flaps. The perforator flaps had higher reexploration rates compared with the nonperforator flaps, but this was not statistically significant (18.4 and 10.6%; p = 0.18). Perforator flaps had a higher flap salvage rate but were not statistically significant (78.6 and 22.2%; p = 0.374). Lastly, although not statistically significant, perforator flaps had a lower rate of complete failure due to anastomotic complications (3.9 and 8.2%; p = 0.336). The meta-analysis included 12 studies (inclusive of the index study) and found no statistical difference in all three outcomes. Conclusion Our meta-analysis is the first reported study and serves as an indication that free perforator flaps in lower extremity are as reliable as their traditional nonperforator counterparts. This does come with the prerequisite appreciation of the anatomical variations, the delicate handling of these flaps, and a low threshold for reexploration.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2GudvoV

Personalized automated treatment planning for breast plus locoregional lymph nodes using Hybrid RapidArc

Publication date: Available online 26 March 2018
Source:Practical Radiation Oncology
Author(s): Mariët J van Duren-Koopman, Jim P Tol, Max Dahele, Ewa Bucko, Philip Meijnen, Ben J Slotman, Wilko FAR Verbakel
PurposeBreast cancer patients who require locoregional lymph node (LLN) irradiation can be treated using a hybrid RapidArc technique combining two tangential and three RapidArc fields. Since the creation of hybrid RapidArc plans is complex and labor-intensive, we developed an automated treatment planning workflow using the scripting application programming interface of the Eclipse treatment planning system.Methods and Materials¹⁵ patients (⁵ right and¹⁰ left-sided) previously treated with breast+LLN radiotherapy were replanned using the script. The automated workflow included: i) optimal placement of the tangential fields based on the planning target volume (PTV) and organ-at-risk (OAR) contours, followed by optimization of field weights and beam energy, ii) positioning of the RapidArc fields, iii) subsequent RapidArc optimization using the RapidPlan knowledge-based planning solution.ResultsAverage total planning times were 163±97 and 33±⁵ minutes for the manual and automated plans, respectively, with approximately 130 and⁵ minutes of user interaction. Dosimetrically, both sets of plans were very similar, with comparable PTV dose homogeneity values and OAR mean dose differences of ≤.¹9Gy. In¹⁴/¹⁵ patients, the physician judged that the automated plan was either preferred (n=⁴) or equal (n=¹⁰) to the manual plan.ConclusionsThe complex hybrid RapidArc planning process for patients requiring breast+LLN irradiation was automated by optimizing the tangential field setup and integrating RapidPlan. The quality of the automated and manual plans was comparable while automated planning times were substantially shorter. The principles described here could be used to automate other planning workflows.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2IUfoK3

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2G8qVaI

Action influences unconscious visual processing

Abstract

It has long been known that action is tightly linked to visual perception. In support of this connection, recent studies have shown that making a simple action towards a visual object can bias subsequent visual processing of features of the acted-on object. The present study examined whether conscious awareness of the acted-on object is necessary to yield this action effect. In two experiments, we found that making an action towards an invisible object resulted in greater priming in a subsequent visual search task. This shows that conscious awareness is not necessary to obtain the action-induced visual bias. More importantly, the result implies that action might amplify the sensory signal from the subliminally presented object, which is presumed to occur during early visual processing.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Gvu6c0

Effects of absolute luminance and luminance contrast on visual search in low mesopic environments

Abstract

Diverse adaptive visual processing mechanisms allow us to complete visual search tasks in a wide visual photopic range (>0.6 cd/m²). Whether search strategies or mechanisms known from this range extend below, in the mesopic and scotopic luminance spectra (<0.6 cd/m²), has yet to be addressed. Based on a study that addressed simple target discrimination in luminance environments using contrast-dependent behavioral efficiency functions, we assessed visual search in more complex-feature and conjunction-search paradigms. The results verify the previously reported deficiency windows defined by an interaction of base luminance and luminance contrast for more complex visual-search tasks. Based on significant regression analyses, a more precise definition of the magnitude of contribution of different contrast parameters. Characterized feature search patterns had approximately a 2.5:1 ratio of contribution from the Michelson contrast property relative to Weber contrast, whereas the ratio was approximately 1:1 in a serial-search condition. The results implicate near-complete magnocellular isolation in a visual-search paradigm that has yet to be demonstrated. Our analyses provide a new method of characterizing visual search and the first insight in its underlying mechanisms in luminance environments in the low mesopic and scotopic spectra.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Gr8E89

Psychophysics with children: Investigating the effects of attentional lapses on threshold estimates

Abstract

When assessing the perceptual abilities of children, researchers tend to use psychophysical techniques designed for use with adults. However, children's poorer attentiveness might bias the threshold estimates obtained by these methods. Here, we obtained speed discrimination threshold estimates in 6- to 7-year-old children in UK Key Stage 1 (KS1), 7- to 9-year-old children in Key Stage 2 (KS2), and adults using three psychophysical procedures: QUEST, a 1-up 2-down Levitt staircase, and Method of Constant Stimuli (MCS). We estimated inattentiveness using responses to "easy" catch trials. As expected, children had higher threshold estimates and made more errors on catch trials than adults. Lower threshold estimates were obtained from psychometric functions fit to the data in the QUEST condition than the MCS and Levitt staircases, and the threshold estimates obtained when fitting a psychometric function to the QUEST data were also lower than when using the QUEST mode. This suggests that threshold estimates cannot be compared directly across methods. Differences between the procedures did not vary significantly with age group. Simulations indicated that inattentiveness biased threshold estimates particularly when threshold estimates were computed as the QUEST mode or the average of staircase reversals. In contrast, thresholds estimated by post-hoc psychometric function fitting were less biased by attentional lapses. Our results suggest that some psychophysical methods are more robust to attentiveness, which has important implications for assessing the perception of children and clinical groups.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DWWAWL

Memory guidance in distractor suppression is governed by the availability of cognitive control

Abstract

Information stored in the memory systems can affect visual search. Previous studies have shown that holding the to-be-ignored features of distractors in working memory (WM) could accelerate target selection. However, such facilitation effect was only observed when the cued to-be-ignored features remained unchanged within an experimental block (i.e., the fixed cue condition). No search benefit was obtained if the to-be-ignored features varied from trial to trial (i.e., the varied cue condition). In the present study, we conducted three behavioral experiments to investigate whether the WM and long-term memory (LTM) representations of the to-be-ignored features could facilitate visual search in the fixed cue (Experiment 1) and varied cue (Experiments 2 and 3) conditions. Given the importance of the processing time of cognitive control in distractor suppression, we divided visual search trials into five quintiles based on their reaction times (RTs) and examined the temporal characteristics of the suppression effect. Results showed that both the WM and LTM representations of the to-be-ignored features could facilitate distractor suppression in the fixed cue condition, and the facilitation effects were evident across the quintiles in the RT distribution. However, in the varied cue condition, the RT benefits of the WM-matched distractors occurred only in the trials with the longest RTs, whereas no advantage of the LTM-matched distractors was observed. These results suggest that the effective WM-guided distractor suppression depends on the availability of cognitive control and the LTM-guided suppression occurs only if sufficient WM resource is accessible by LTM reactivation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2I4b49K

Promoting Conditional Use of Communication Skills for Learners With Complex Communication Needs: A Tutorial

Purpose

Conditional use of communication skills refers to the ability of a learner to appropriately generalize and discriminate when, where, and how to communicate based on constant variation and shifts in environmental cues.

Method

We describe discrimination and generalization challenges encountered by learners with complex communication needs and ways in which these challenges are fostered through traditional communication intervention programming. We address arrangements in instruction that maximize the probability of learners acquiring the conditional use of new vocabulary and the modest instructional technology implemented when planning for generalization.

Results

We propose establishing well-discriminated and generalized use of new vocabulary items through the application of a general case instruction framework to communication intervention programming.

Conclusion

We provide intervention methodology, including intervention steps for general case instruction, a plethora of functional examples, and graphic displays to assess and intervene to promote conditional use of communication skills for learners with complex communication needs.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2DWPAZO