Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174: 08/01/17

Τρίτη 1 Αυγούστου 2017

A comparison of the tongue-in-groove and columellar strut in creating and maintaining tip projection and rotation: a randomized single blind trial

Abstract

Background

Rhinoplasty is one of the most challenging esthetic operations. The ability to achieve precise and predictable changes in the shape and position of the nasal tip is still among the demanding areas of rhinoplasty. Tongue in groove (TIG) and columellar strut are two of the many techniques to ensure an adequate nasal tip projection and rotation; however, there is little evidence to support long-term efficacy of these techniques.

Methods

In a clinical trial, 80 cases who were rhinoplasty candidates were studied prospectively. They were randomly divided into two groups according to the use of columellar strut and TIG. The outcome measures were gaining and maintaining tip projection and rotation in the long term. Standardized photographs before and 6 and 12 months after the surgery were the measurements to compare the results between the two groups, which were evaluated for nasolabial angle and projection. Also, the patients' satisfaction with beauty and nasal obstruction were assessed using the VAS (Visual Analogue Scale).

Results

Forty patients were operated using the columellar strut technique while the TIG method was used in 40 cases. Preoperatively, tip rotation, tip projection, and other characteristics were not significantly different between the two groups. Postoperatively, the patients' esthetic satisfaction was significantly greater in the TIG group 6 and 12 months after the surgery (P value = 0.001). The rest of the evaluated variables did not have any significant differences between the two groups.

Conclusions

It seems that both columellar strut and tongue in groove methods are effective techniques in maintaining tip projection and/or rotation in rhinoplasty. Using the tongue in groove technique in qualified hands may give significantly better esthetic satisfaction to patients than the columellar strut technique.

Level of evidence: Level I, therapeutic study.

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First reported case of magnesium-made bioresorbable scaffold to treat spontaneous left anterior descending coronary artery dissection

Abstract

Spontaneous coronary artery dissection (SCAD) is a rare cause of Acute Coronary Syndrome. Although its treatment is still debated, use of Bioreasorbable Scaffold was recently advocated as an attractive option in this setting. We report the first case, to our knowledge, of a new magnesium-made Bioresorbable Scaffold implantation in a young woman presenting with Non-ST- Elevation Myocardial Infarction and a rapid worsening SCAD.

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Doppler echocardiography underestimates the prevalence and magnitude of mid-cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy

Abstract

Objectives

To evaluate utility of Doppler echocardiography in the assessment of left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM).

Background

LVMCO is a relatively under-diagnosed complication of HCM and may occur alone or in combination with LV outflow tract obstruction (LVOTO). Identifying and quantifying LVMCO and differentiating it from LVOTO has important implications for patient management. We aimed to assess diagnostic performance of Doppler echocardiography in the assessment of suspected LV obstruction.

Methods

Forty symptomatic HCM patients with suspected obstruction underwent cardiac catheterization, and comparison of location and magnitude of Doppler derived gradients with synchronous invasive measurements (reference standard), at rest and isoprenaline stress (IS).

Results

Doppler's diagnostic accuracy for any obstruction (≥30 mmHg) in this cohort was 75% with false positive and false negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the accuracy is only 50%, with false positive and false negative rates of 10 and 40%, respectively.

Doppler gradients for isolated LVOTO were similar to invasive: 85 ± 51 and 87 ± 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO were consistently lower than invasive: 45 ± 38 and 81 ± 31 mmHg, respectively (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral signals were identified as causes of Doppler-derived inaccuracies.

Conclusions

Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and invasive measurements may improve detection of LVMCO in HCM.

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Techniques and outcomes of paravalvular leak repair after transcatheter aortic valve replacement

Abstract

Objectives

To investigate the feasibility, procedural success, and outcomes of paravalvular leak (PVL) closure in patients with prior transcatheter aortic valve replacement (TAVR).

Background

PVL after TAVR is associated with adverse patient outcomes and increased mortality. Percutaneous PVL closure has emerged as a therapeutic strategy for addressing this issue, but data for transcatheter PVL repair after TAVR remains limited.

Methods

This is a single center retrospective review of PVL closure after TAVR. Patients with balloon-expandable or self-expanding prostheses were included. Baseline patient demographics, procedural characteristics, complications, and clinical outcomes were reviewed.

Results

A total of 18 patients with clinically significant PVL after TAVR referred for PVL closure were identified during the study period. Procedural success resulting in successful transcatheter occluder plug delivery was 78% (14 cases). Balloon postdilatation (2/4) and valve-in-valve (2/4) were used effectively in the remaining patients after an unsuccessful PVL closure attempt. PVL grading by echocardiography decreased from moderate or severe to < moderate in 13 patients (72%). Adverse events including cardiac tamponade and acute kidney injury occurred in 1 case each. One-month all-cause mortality was 11%.

Conclusion

In selected patients, percutaneous PVL repair following TAVR is feasible and effective for both balloon-expandable and self-expanding prostheses. Most patients undergoing PVL closure after TAVR require a single occluder plug placement for reduction in PVL to mild or less.

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Transulnar cardiac catheterization and percutaneous coronary intervention: techniques, transradial comparisons, anatomical considerations, and comprehensive literature review

Abstract

Ulnar arterial access for cardiac catheterization and intervention is an alternative approach compared with radial or femoral access. Ulnar access is infrequently performed since the radial artery is readily palpable and is commonly used worldwide to minimize vascular complications from femoral access. Nevertheless, ulnar access provides a suitable access site in patients who are poor candidates for femoral access, have pre-existing radial occlusion, radial artery hypoplasia or hyperplasia from prior radial artery procedures, radial stenosis, radial loops, radial tortuosity, small radial arteries, and/or have future need for radial graft for dialysis or coronary artery bypass graft. Furthermore, femoral access is the standard default option if radial access fails. Consequently, learning ulnar access provides a suitable forearm alternative to avoid femoral access when deemed high risk or undesirable. This review discusses the techniques of ulnar access, advantages and disadvantages of ulnar versus radial access, the clinical trials on ulnar cardiac catheterization and its associated complications.

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Transseptal puncture using surgical electrocautery in children and adults with and without complex congenital heart disease

Abstract

Background

Atrial transseptal puncture (TSP) for cardiac catheterization procedures remain challenging in children and adults with complex congenital heart disease (CHD).

Objectives

We sought to evaluate our experience using radiofrequency (RF) current via surgical electrocautery needle for TSP to facilitate diagnostic and interventional procedures.

Methods

Retrospective chart review of all patients (pts) who underwent TSP using RF energy (10–25 W) via surgical electrocautery from three centers from January 2011 to January 2017 were evaluated. Echocardiograms were reviewed to define the atrial septum as normal and complex (thin aneurysmal, thick/fibrotic, synthetic patch material, and extra cardiac conduit).

Results

A total of 54 pts underwent 55 successful TSP. Median age was 12.5 years (1 day–54 years) and weight was 52.7 kg (2–162). Indications for TSP included; EP study and ablation procedures in structurally normal hearts (n = 24) and in complex atrial septum/CHD and structural heart disease pts (n = 30): Electrophysiology study and ablation in 4, diagnostic catheterization in 9, and interventional procedures in 17 pts were performed. Atrial TSP was successful in 54/55 (98%). Atrial perforation with tiny-small pericardial effusion not requiring intervention was noted in 2 pts. TSP was unsuccessful in one critically ill neonate with unobstructed TAPVR and restricted atrial septum who experienced cardiac arrest requiring CPR, ECMO, and emergent surgery.

Conclusions

RF current delivery using surgical electrocautery for TSP is a feasible and an effective option in patients with complex CHD for diagnostic, interventional, and electrophysiology procedures.

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Coronary atherectomy is associated with improved procedural and clinical outcomes among patients with calcified coronary lesions: Insights from the VA CART program

Abstract

Objectives

We sought to evaluate the prevalence of calcified coronary lesions and the association between the use of atherectomy and clinical outcomes.

Background

Calcified coronary arteries are associated with an increased risk of procedural complications during percutaneous coronary intervention (PCI). The outcomes of coronary atherectomy for adjunctive treatment of calcified coronary lesions are not well described.

Methods

We identified all patients treated for calcified coronary lesions at VA hospitals. A propensity weighted cohort was created for those treated with or without adjunctive atherectomy to evaluate the complications and outcomes between groups.

Results

From 2007 to 2015, 9,719 patients underwent single-vessel PCI for treatment of naïve native calcific coronary lesions. The proportion of patients undergoing revascularization of calcified lesions increased over the study period (P = 0.03) and 1,731 patients (18%) were treated with atherectomy. Adjunctive atherectomy was more likely to be used in high-risk lesions (76.5% vs. 46.8%, P < 0.001). After propensity weighting, coronary atherectomy was associated with a 38% decrease in the odds of procedural complications and a 54% decrease in the odds of clinical complications (both P = 0.005). There was no difference in rates of 2-year death (HR: 1.07; 95% CI: 0.92–1.24), myocardial infarction (HR: 0.96; 95% CI: 0.75–1.23) or target vessel revascularization (HR: 0.96; 95% CI: 0.78–1.19)

Conclusions

Percutaneous treatment of calcified coronary lesions has increased over time. The adjunctive use of coronary atherectomy was associated with a reduction in procedural complications among patients with calcified coronary arteries. Two-year TVR, MI and overall mortality were similar between the two groups.

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The relationship between the basal coronary translesional pressure gradient and fractional flow reserve

Aim

Fractional flow reserve (FFR) allows for physiological definition of coronary lesion severity but requires induction of maximal coronary circulation hyperemia with administration of adenosine leading to coronary resistive vessel vasodilatation. However, the hyperemic response to adenosine, and therefore the calculation of FFR, may be affected by dysfunction of the coronary microvasculature. The aim was to define the relationship between basal P_d/P_a and FFR and identify lesion-independent predictors of the change in P_d/P_a with hyperemia.

Methods and Results

One hundred and sixty-six consecutive patients undergoing FFR measurement were prospectively enrolled (mean age 62.6 ± 10.3 years, 27% females). Basal P_d/P_a, FFR, and delta P_d/P_a (difference between basal P_d/P_a and FFR) were recorded. Independent predictors of delta P_d/P_a included angiographic lesion severity, lesion length, gender, body mass index, and total cholesterol:HDL cholesterol ratio. The best basal P_d/P_a cutoff value to predict lesion physiological significance was 0.87 (positive predictive value of 100% for an FFR value ≤0.80) and the best cutoff for nonsignificance was 0.93 (negative predictive value of 98% for an FFR value >0.80).

Conclusion

The delta P_d/P_a may be affected by patient gender, body mass index, and cholesterol profile. A basal P_d/P_a value of ≥0.93 is highly predictive of an FFR >0.80. Conversely, a basal P_d/P_a value of ≤0.87 is highly predictive of an FFR ≤0.80. © 2017 Wiley Periodicals, Inc.

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Factors associated with performing urgent coronary angiography in out-of-hospital cardiac arrest patients

Abstract

Objectives

Factors associated with performing urgent coronary angiography (UCA) in patients with out-of-hospital cardiac arrest (OHCA) were identified.

Background

Current guidelines for resuscitated OHCA patients recommend UCA if there is ST-elevation on post-arrest electrocardiogram or high suspicion of acute myocardial infarction. Some have advocated for UCA in all OHCA regardless of suspected etiology. The reasons for variations in performing UCA are not well understood.

Methods

A retrospective analysis of subjects presenting with resuscitated OHCA to a single academic medical center from 12/15/2007 to 8/31/2014 was conducted. Demographic and clinical characteristics of patients undergoing UCA, defined as angiography within 6 hr of presentation, were compared with those not undergoing UCA. Logistic regression was used to determine predictors of UCA.

Results

A total of 323 resuscitated OHCA patients (mean age, 64 years; women, 35%) were included in the analysis; 107 (33.1%) underwent coronary angiography during their hospitalization and 66 (20.4%) underwent UCA. Multivariable adjusted factors associated with UCA were ST-elevation [odds ratio (OR) 14.66, 95% confidence interval (CI) 6.28–34.24, P < 0.001], initial shockable rhythm (OR 3.69, 95% CI 1.52–8.97, P = 0.004), and history of coronary artery disease (CAD) (OR 3.37, 95% CI 1.43–7.95, P = 0.005). Higher age (OR 0.71 per decade, 95% CI 0.55–0.92, P = 0.01) and obvious non-cardiac cause of arrest (OR 0.08, 95% CI 0.02–0.38, P = 0.001) were negatively associated with UCA.

Conclusions

In resuscitated out-of-hospital cardiac arrest patients, ST-elevation, shockable rhythm, and history of CAD were associated with performing urgent coronary angiography; older patients and those with obvious non-cardiac causes of arrest were negatively associated.

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Angiographic and clinical performance of polymer-free biolimus-eluting stent in patients with ST-segment elevation acute myocardial infarction in a metropolitan public hospital: The BESAMI MUCHO study

Abstract

Objectives

This study aimed at assessing the performance of a new generation polymer-free biolimus-eluting stent (BES) in real-world patients with ST-segment elevation myocardial infarction (STEMI).

Background

Polymers components of early-generation drug-eluting stents have been implicated in the pathogenesis of delayed arterial healing, vessel remodeling, and delayed stent thrombosis. Recently, a novel polymer-free BES has shown excellent clinical performance in clinical trial setting.

Methods

Overall, 175 consecutive patients (64 ± 14 years, 141 men) treated with the BioFreedom (Biosensors Europe, Morges, Switzerland) polymer-free BES because of STEMI were included in this study. The primary endpoint was the rate of major adverse cardiac events (MACE), a composite of cardiac death, recurrent myocardial infarction, and ischemia-driven target vessel revascularization at 1 year follow-up. A subgroup of patients underwent 6-month angiographic follow-up. Dual antiplatelet therapy was prescribed for 12 months after STEMI.

Results

At 1 year, the cumulative rate of MACE was 4.6%. One patient (0.6%) had an arrhythmic cardiac death and five (2.9%) had ischemia-driven target vessel revascularization, although only three (1.7%) had target lesion revascularization. Two (1.1%) patients had acute stent thrombosis yielding nonfatal myocardial infarction. In 70 patients (63 ± 14 years, 61 men), quantitative coronary angiography at 6-month follow-up revealed diameter stenosis of 24.1 ± 13.7% and minimal lumen diameter of 2.29 ± 0.56 mm, yielding a late lumen loss of 0.13 ± 0.14 mm.

Conclusions

In real-world setting, implantation of a new-generation polymer-free BES during STEMI is associated with favorable clinical and angiographic results, pointing toward the overall efficacy and safety of the device in complex clinical scenarios.

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Simulation-based education leads to decreased use of fluoroscopy in diagnostic coronary angiography

Abstract

Objectives

The aim of this study is to determine whether simulation-based education (SBE) translates into reduced procedure time, radiation, and contrast use in actual clinical care.

Background

As a high volume procedure often performed by novice cardiology fellows, diagnostic coronary angiography represents an excellent target for SBE. Reports of SBE in interventional cardiology are limited and there is little understanding of the potential downstream clinical impact of these interventions.

Methods

All diagnostic coronary angiograms performed at a single center between January 1, 2011 and June 30, 2015 were analyzed. Random effects linear regression models were used to compare outcomes between procedures performed by 12 cardiology fellows who underwent simulation-based training and those performed by 20 traditionally trained fellows.

Results

Thirty-two cardiology fellows performed 2,783 diagnostic coronary angiograms. Procedures performed by fellows trained with SBE were shorter (mean of 23.98 min vs. 24.94 min, P = 0.034) and were performed with decreased radiation (mean of 56,348 mGycm² vs. 66,120 mGycm², P < 0.001). After controlling for year in training, procedure year, access site, and supervising attending physician, training on the simulator was independently associated with 117 fewer seconds of fluoroscopy time per procedure (P = 0.04).

Conclusions

Diagnostic coronary angiography SBE is associated with decreased use of fluoroscopy in downstream clinical care. SBE may be a useful tool to reduce radiation exposure in the cardiac catheterization laboratory

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Bivalirudin in percutaneous coronary intervention for chronic total occlusion: A single-center pilot study

Abstract

Background

Bivalirudin has been reported to be an alternative to unfractionated heparin (UFH) for anticoagulation during percutaneous coronary intervention (PCI) and associated with less bleeding risk. However, the feasibility of bivalirudin during PCI of chronic total occlusion lesions (CTO) remains unknown.

Objective

To evaluate the efficacy and safety of bivalirudin versus UFH in CTO PCI. Methods: In this prospective and randomized controlled trial in single center, CTO patients with high bleeding risk were randomized to treatment with bivalirudin (bolus 0.75 mg/kg followed by infusion of 1.75, extra bolus 0.3 mg/kg before stenting) or UFH (100 IU/kg). The primary efficacy end point was the incidence of major adverse cardiac events (MACEs, composite of all-cause mortality, cardiac death, stent thrombosis, periprocedural myocardial infarction, or additional unplanned target lesion revascularization, or any other post-PCI ischemic event) in-hospital, and at 1-year follow-up. The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI.

Results

A total of 84 high bleeding risk patients undergoing PCI for CTO lesions were enrolled. The baseline characteristics were similar in both treatment arms. In hospital MACEs rates were 21.4% in the bivalirudin group and 14.3% in the UFH group (P = 0.393). During 1-year's follow-up, end points did not significantly differ between the groups either. Occurrence of the major bleeding events were 4.8% in the bivalirudin group and 9.5% in the UFH group (P = 0.676). No entry-site complication was observed.

Conclusion

In CTO patients at high risk for bleeding undergoing PCI, our data indicates that bivalirudin appears to be at least comparable in efficacy and safety to UFH. A larger clinical trial should be designed to further elucidate its efficacy and safety.

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Efficacy of a novel swallowing exercise program for chronic dysphagia in long-term head and neck cancer survivors

Abstract

Background

The efficacy of rehabilitative exercises for chronic dysphagia treatment in head and neck cancer survivors has not been studied extensively and is ambiguous.

Methods

A prospective clinical phase II study using an intensive strength training program was carried out in 17 head and neck cancer survivors with chronic dysphagia. Both swallow and nonswallow exercises were performed for 6-8 weeks with a newly developed tool allowing for progressive muscle overload, including chin tuck, jaw opening, and effortful swallow exercises. Outcome parameters were feasibility, compliance, and parameters for effect.

Results

Feasibility in terms of the program completion rate was 88%. Compliance with the exercises was 97%. After the training period, chin tuck, jaw opening, and anterior tongue strength had substantially improved. All but 1 patient reported to benefit from the exercises.

Conclusion

Feasibility and compliance were high. Some objective and subjective effects of progressive load on muscle strength and swallowing function could be demonstrated.

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Symptom burden and patient characteristics: Association with quality of life in patients with head and neck cancer undergoing radiotherapy

Abstract

Background

Patients with head and neck cancer (HNC) experience diminished quality of life (QOL) during and after treatment. This study examined which characteristics were associated with QOL over time.

Methods

One hundred thirty-three patients with HNC from a study of 534 oncology patients rated physical and mental QOL using the Short Form-12 5 times from the initiation of radiotherapy (RT) through the following 6 months. Linear mixed model analyses examined changes over time and associated characteristics.

Results

The QOL deteriorated during RT and gradually improved after completion. Less social support was negatively associated with both physical and mental QOL. Older age, more comorbidities, more psychological symptoms, and concomitant chemotherapy (CTX) were negatively associated with physical QOL. Male sex, less physical symptoms, surgery before RT, and concomitant chemotherapy were positively associated with mental QOL.

Conclusion

Clinicians can use knowledge on time course and associated characteristics to identify and inform patients at higher risk for diminished QOL.

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Efficacy of a novel swallowing exercise program for chronic dysphagia in long-term head and neck cancer survivors

Abstract

Background

The efficacy of rehabilitative exercises for chronic dysphagia treatment in head and neck cancer survivors has not been studied extensively and is ambiguous.

Methods

Results

Conclusion

Feasibility and compliance were high. Some objective and subjective effects of progressive load on muscle strength and swallowing function could be demonstrated.

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Symptom burden and patient characteristics: Association with quality of life in patients with head and neck cancer undergoing radiotherapy

Abstract

Background

Patients with head and neck cancer (HNC) experience diminished quality of life (QOL) during and after treatment. This study examined which characteristics were associated with QOL over time.

Methods

Results

Conclusion

Clinicians can use knowledge on time course and associated characteristics to identify and inform patients at higher risk for diminished QOL.

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Cystic Fibrosis Prognosis - News-Medical.net

Cystic Fibrosis Prognosis
News-Medical.net
Other organs affected include the pancreas, intestines, liver, sinuses, and reproductive organs. ... Chronic renal insufficiency, hypertriglyceridemia, and colon cancer are found to occur more commonly in adults with cystic fibrosis than in those ...

and more »

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Optical Loupes: A Useful Tool for the Oncall Otorhinolaryngologist—Our Experience

Abstract

We aimed to evaluate the efficacy and utility of loupes for ENT on-calls. We conducted a 2 month prospective clinical study using loupes during on-calls. We examined patients twice, with and without loupes and compared visibility and diagnostic ease. We used the loupes in a total of 71 patients for a variety of ENT emergencies. We found that visibility and diagnostic ease was improved in all cases. During procedures we found that improved visibility led to better instrument placement and more satisfactory outcomes. Loupes have been previously used intra-operatively with good results. The obstacles to wider usage are reportedly the expense and learning curve required. We have acquired some cheap loupes and have found evidence that earlier usage eases the transition. We have found that they are a useful addition to the on-call ENT armoury as they facilitate superior visibility and improved instrument placement.

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Oral status, quality of life, and anxiety and depression in hemodialysis patients and the effect of the duration of treatment by dialysis on these variables

Abstract

This study aimed is to evaluate the oral health status, quality of life, anxiety and depression among hemodialysis patients and to analyze the effect of the duration of dialysis on these variables. 120 patients on hemodialysis and 120 control subjects underwent oral examination, periodontal evaluation, xerostomia study using a Visual Analogue Scale (VAS), sialometry evaluation; quality of life (QOL) using the OHIP-14 questionnaire and anxiety/depression. Bleeding index, CPTIN, clinical attachment level, and probing depth were significantly higher in the hemodialysis group than the control group (p < 0.001). VAS scores were higher in patients on hemodialysis with significant differences in 6 of the 8 domains (p ≤ 0.05). Unstimulated whole saliva was significantly lower in hemodialysis patients than control subjects (p < 0.001). OHIP-14 scores showed significantly poorer QOL in patients on hemodialysis than control subjects (p = 0.042). Hemodialysis patients presented greater depression and anxiety than control (p < 0.001). Periodontal health was worse among the patients who had been in treatment >10 years, xerostomia and sialorrea was worse in patients treated for 5–9.9, and >10 years, QOL was worse in patients who had spent <1 year; depression and anxiety was greater among those treated for 1–2.9 years. In conclusion, Oral health, QOL, anxiety and depression are worse in patients on hemodialysis, and oral health deteriorates as the time spent in dialysis lengthens, but patients in treatment for <3 years presented the poorest QOL and the greatest anxiety and depression.

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Spatial orientation: New model for the origin of grid cells - Science Daily

Spatial orientation: New model for the origin of grid cells
Science Daily
The members of these groups become active when the animal reaches certain locations in space, and they transmit nerve impulses in precisely coordinated temporal sequences, which follow a particular rhythmic patterns, and thereby encode relative spatial ...

and more »

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Thyroid disorder in women - Himalayan Times

Thyroid disorder in women
Himalayan Times
And the tragic part is that they are not well informed about the reason of such rampant rise of thyroid problem in recent days. It has been evidently proven that the frequency of thyroid cancer in women is considerably higher than that in men. In Nepal ...

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Differentiated Thyroid Cancer Therapeutics Market Predicted ... - Monotone Critic

Monotone Critic

Differentiated Thyroid Cancer Therapeutics Market Predicted ...
Monotone Critic
Differentiated thyroid cancer is divided into follicular and papillary thyroid cancer according to the studies by the WHO thyroid cancer therapeutics.
New Study Offers Detailed Insights on Differentiated Thyroid Cancer ...Find Market Research By Abhishek Budholiya (press release) (blog)

all 2 news articles »

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Gastroparesis

Gastroparesis: A disease of the muscles of the stomach or the nerves controlling the muscles that causes the muscles to stop working. Gastroparesis results in inadequate grinding of food by the stomach and poor emptying of food from the stomach into the intestine. Gastroparesis may be associated with paralysis of the small intestine and colon. The most common underlying cause is diabetes mellitus. Gastroparesis is diagnosed via gastric emptying study. It is usually treated with medications that stimulate the stomach muscle to contract.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Optical Loupes: A Useful Tool for the Oncall Otorhinolaryngologist—Our Experience

Abstract

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Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle-invasive bladder cancer

Abstract

Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages. Pathways globally dysregulated in cancer relative to normal urothelium included glucose, tricarboxylic acid (TCA) cycle, lipid, amino acid, and nucleotide pathways. Urothelial carcinoma showed elevated glucose utilization for glycolysis and increased sorbitol pathway intermediates, consistent with Warburg effect. Anaplerosis to sustain energy production suggested by increased late TCA cycle intermediates, amino acids, and dipeptides occurs in bladder cancer. Urothelial carcinoma also shows altered membrane lipid membrane metabolism and differential derivation of nucleic acid components pyrimidine and purine. In stage comparison, MIBC appears to preferentially enhance cyclooxygenase (COX) and lipoxygenase (LOX) signaling, increase heme catabolism, and alter nicotinamide adenine dinucleotide (NAD+) synthesis with a possible influence from associated inflammatory cells. We identify numerous metabolomic alterations in NMIBC and MIBC that likely reflect underlying pathway changes. Differential pathway activity may have value in designing stage-specific novel therapeutics in urothelial carcinoma.

Using a highly sensitive metabolomics approach, we identified multiple pathway changes between normal urothelium and high-grade urothelial carcinoma and between high-grade carcinomas of different stages. Several of these differential metabolite profiles suggest the potential for unique targeted therapy in NMIBC and MIBC populations.

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Small cell lung carcinoma cell line screen of etoposide/carboplatin plus a third agent

Abstract

The SCLC combination screen examined a 9-point concentration response of 180 third agents, alone and in combination with etoposide/carboplatin. The predominant effect of adding a third agent to etoposide/carboplatin was additivity. Less than additive effects occurred frequently in SCLC lines sensitive to etoposide/carboplatin. In SCLC lines with little or no response to etoposide/carboplatin, greater than additive SCLC killing occurred over the entire spectrum of SCLC lines but never occurred in all SCLC lines. Exposing SCLC lines to tubulin-targeted agents (paclitaxel or vinorelbine) simultaneously with etoposide/carboplatin resulted primarily in less than additive cell killing. As single agents, nuclear kinase inhibitors including Aurora kinase inhibitors, Kinesin Spindle Protein/EG5 inhibitors, and Polo-like kinase-1 inhibitors were potent cytotoxic agents in SCLC lines; however, simultaneous exposure of the SCLC lines to these agents along with etoposide/carboplatin, generally, resulted in less than additive cell killing. Several classes of agents enhanced the cytotoxicity of etoposide/carboplatin toward the SCLC lines. Exposure of the SCLC lines to the MDM2 inhibitor JNJ-27291199 produced enhanced killing in 80% of the SCLC lines. Chk-1 inhibitors such as rabusertib increased the cytotoxicity of etoposide/carboplatin to the SCLC lines in an additive to greater than additive manner. The combination of GSK-3β inhibitor LY-2090314 with etoposide/carboplatin increased killing in approximately 40% of the SCLC lines. Exposure to the BET bromodomain inhibitor MK-8628 increased the SCLC cell killing by etoposide/carboplatin in 20–25% of the SCLC lines. Only 10–15% of the SCLC lines had an increased response to etoposide/carboplatin when simultaneously exposed to the PARP inhibitor talazoparib.

Sixty-three human small cell lung cancer cell lines were screened to search for agents which may act synergistically with etoposide/carboplatin. Most third agents were additive or antagonistic with etoposide/carboplatin. Third agents which were synergistic are highlighted.

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Identification of sentinel lymph nodes by contrast-enhanced ultrasonography with Sonazoid in patients with breast cancer: a feasibility study in three hospitals

Abstract

The aim of this prospective study was to evaluate the feasibility of periareolar injection of the contrast agent Sonazoid (SNZ) followed by ultrasonography (US) for the identification of sentinel lymph node (SLN) in breast cancer patients with clinically negative node. Patients (n = 100) with T1-2N0M0 breast cancer received a periareolar injection of SNZ followed by US to identify contrast-enhanced SLN. Each contrast-enhanced SLN underwent fine needle aspiration cytology (FNAC) followed by SLN biopsy with a conventional method using blue dye and/or radiocolloid (B/R). In almost all cases, contrast-enhanced lymphatic vessels were clearly visualized by US soon after the periareolar injection of SNZ and the SLNs were easily identified with an identification rate of 98% (98/100) for SNZ and 100% (100/100) for B/R. The number of SLNs identified by SNZ (SNZ-SLN) (mean per patient, 1.52) was significantly lower than that identified by B/R (B/R-SLN) (2.19) (P < 0.0001). Twenty-five patients with positive SLNs had at least one positive SNZ-SLN. On a node-by-node basis, sensitivity, specificity, and accuracy of FNAC for SNZ-SLNs (n = 149) were 33.3%, 99.2%, and 85.9%, respectively. Identification of SLN by periareolar injection of SNZ is a technically simple method with an identification rate as high as 98%. SNZ-SLN thus seems to be a good target for FNAC, but sensitivity of FNAC for SNZ-SLNs needs to be improved.

Patients (n = 100) received periareolar injection of Sonazoid followed by ultrasonography of the axilla for identification of contrast-enhanced sentinel lymph node (SLN). This method is technically simple with a high success rate (98%) and comparable to the conventional method using blue dye and/or radiocolloid.

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Botulinum Toxin Injections Into the Lateral Cricoarytenoid Muscles for Vocal Process Granuloma

Contact granulomas are benign, exophytic inflammatory lesions of the larynx that typically arise on or near the vocal process of the arytenoid cartilage. The most common management options include voice therapy and antireflux pharmacotherapy, intralesional steroid injections, botulinum toxin injections, and surgical excision. In-office Botox injection into the lateral cricoarytenoid (LCA) muscle can be effective even for recurrent granulomas.

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Cordyceps Sinensis: Anti-fibrotic and inflammatory effects of a cultured polysaccharide extract

Publication date: Available online 1 August 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Danfei Huang, Soma Meran, Shao-Ping Nie, Adam Midgley, Junqiao Wang, Steve W. Cui, Mingyong Xie, Glyn O. Phillips, Aled O. Phillips
It has been suggested that the traditional Chinese herbal preparation Cordyceps Sinensis (CS) may have a beneficial effect in renal disease. To satisfy increasing demand, CS derivatives have been produced by aseptic mycelia cultivation. We have demonstrated antifibrotic activity of cultured CS previously. The aim of this study was to examine bioactivity of a polysaccharide isolated from cultured CS with a complicated monosaccharide composition, mainly consisting of Gal, Glc and Man.This polysaccharide antagonised the effect of TGF-β1 in stimulating the expression of collagen in the HK2 renal cell line. This was associated with down regulation of the TGF-β receptor Alk5. In addition the polysaccharide antagonised IL-1β stimulated sICAM-1 dependent adherence of monocytes to a monolayer of HK2 cell. This was associated with increased expression of the primary receptor for hyaluronan CD44, and was abrogated by removal of the cell surface hyaluronan pericellular coat.In summary we describe both anti-fibrotic and anti-inflammatory activity in a polysaccharide isolated from cultured CS.

Graphical abstract

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Sequential segmental analysis of the crocodilian heart

Abstract

Differences between hearts of crocodilians and those of mammals and birds are only partly understood because there is no standardised approach and terminology for describing cardiac structure. Whereas most reptiles have an undivided ventricle, crocodilians have a fully septated ventricle. Their hearts, therefore, are more readily comparable with the hearts of mammals and birds. Here, we describe the heart of a crocodile (Crocodylus noliticus). We use the versatile sequential segmental approach to analysis, juxtaposing several key views of the crocodilian heart to the comparable views of human hearts. In crocodiles, the atrial and ventricular septums are complete but, unlike in placental mammals, the atrial septum is without an oval fossa. The myocardial component of the crocodilian ventricular septum dominates, but the membranous septum likely makes up a greater proportion than in any mammal. In the crocodile, the aortic trunk takes its origin from the left ventricle and is not wedged between the atrioventricular junctions. Consequently, there is a common atrioventricular junction, albeit with separate right and left atrioventricular valvar orifices. As in mammals, nonetheless, the crocodilian left atrioventricular valvar orifice is cranial to the right atrioventricular valvar orifice. By applying a method of analysis and terminology usually restricted to the human heart, we build from the considerable existing literature to show neglected and overlooked shared features, such as the offset between the left and right atrioventricular valvar orifices. Such commonalities are surprising given the substantial evolutionary divergence of the archosaur and synapsid lineages, and likely reflect evolutionarily shared morphogenetic programmes.

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Outcome and toxicity of radical radiotherapy or concurrent Chemoradiotherapy for elderly cervical cancer women

Concurrent chemoradiotherapy (CCRT) is the standard treatment for local advanced cervical cancer. However, for elderly patients, studies are limited and the outcomes are controversial. We retrospectively analy...

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Screening the ToxCast phase II libraries for alterations in network function using cortical neurons grown on multi-well microelectrode array (mwMEA) plates

Abstract

Methods are needed for rapid screening of environmental compounds for neurotoxicity, particularly ones that assess function. To demonstrate the utility of microelectrode array (MEA)-based approaches as a rapid neurotoxicity screening tool, 1055 chemicals from EPA's phase II ToxCast library were evaluated for effects on neural function and cell health. Primary cortical networks were grown on multi-well microelectrode array (mwMEA) plates. On day in vitro 13, baseline activity (40 min) was recorded prior to exposure to each compound (40 µM). Changes in spontaneous network activity [mean firing rate (MFR)] and cell viability (lactate dehydrogenase and CellTiter Blue) were assessed within the same well following compound exposure. Following exposure, 326 compounds altered (increased or decreased) normalized MFR beyond hit thresholds based on 2× the median absolute deviation of DMSO-treated wells. Pharmaceuticals, pesticides, fungicides, chemical intermediates, and herbicides accounted for 86% of the hits. Further, changes in MFR occurred in the absence of cytotoxicity, as only eight compounds decreased cell viability. ToxPrint chemotype analysis identified several structural domains (e.g., biphenyls and alkyl phenols) significantly enriched with MEA actives relative to the total test set. The top 5 enriched ToxPrint chemotypes were represented in 26% of the MEA hits, whereas the top 11 ToxPrints were represented in 34% of MEA hits. These results demonstrate that large-scale functional screening using neural networks on MEAs can fill a critical gap in assessment of neurotoxicity potential in ToxCast assay results. Further, a data-mining approach identified ToxPrint chemotypes enriched in the MEA-hit subset, which define initial structure–activity relationship inferences, establish potential mechanistic associations to other ToxCast assay endpoints, and provide working hypotheses for future studies.

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Biology and management of Avena fatua and Avena ludoviciana : two noxious weed species of agro-ecosystems

Abstract

Avena fatua and Avena ludoviciana are closely related grass weed species infesting a large number of crops around the world. These species are widely distributed in diverse agro-ecosystems from temperate to sub-tropical regions due to their unique seed traits, successful germination ecology, high competitive ability, and allelopathic potential. A. fatua is more widespread, adaptable, and problematic than A. ludoviciana. Both these species infest major winter and spring crops, including wheat, oat, barley, canola, maize, alfalfa, and sunflower, causing up to 70% yield losses depending on crop species and weed density. Chemical control has been challenged by large-scale herbicide resistance evolution in these weed species. A. fatua is the most widespread herbicide-resistant weed in the world, infesting about 5 million hectares in 13 countries. The use of alternative herbicides with different modes of action has proved effective. Several cultural practices, including diverse crop rotations, cover crops, improved crop competition (using competitive cultivars, high seed rates, narrow row spacing, altered crop geometry), and allelopathic suppression, have shown promise for controlling A. fatua and A. ludoviciana. The integrated use of these cultural methods can reduce the herbicide dose required, and lower dependency on herbicides to control these grasses. Moreover, integrated management may successfully control herbicide-resistant populations of these weed species. The use of integrated approaches based on the knowledge of biology and ecology of A. fatua and A. ludoviciana may help to manage them sustainably in the future.

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Oncologic Outcome of Metastasectomy for Urothelial Carcinoma: Who Is the Best Candidate?

Abstract

Background

Resection of metastatic lesions (metastasectomy) is performed for highly selected patients with metastatic urothelial carcinoma (mUC). This study aimed to identify the clinicopathologic factors associated with oncologic outcome for patients who underwent metastasectomy for mUC.

Methods

This analysis included 37 UC patients who underwent metastasectomy with curative intent at nine Japanese hospitals. The primary end point was cancer-specific survival. The Kaplan–Meier method with the log-rank test and the multivariable Cox proportional hazards model addressed the relationship between clinical characteristics and survival.

Results

Metastasectomy was performed for pulmonary (n = 23), nodal (n = 7), and other (n = 7) metastases. The median survival time was 35.4 months (interquartile range [IQR] 15.5, not reached) from the detection of metastasis and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer-specific survival rate after detection of metastasis was 39.7%. In the multivariate analysis, the time from primary surgery to detection of metastasis (time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p = 0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were significantly associated with better survival.

Conclusions

Long-term survival could be achieved for some patients with mUC who underwent metastasectomy. Lung and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP value were identified as associated with survival and should be taken into account when metastasectomy is considered.

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Patterns of Initial Recurrence in Gastric Adenocarcinoma in the Era of Preoperative Therapy

Abstract

Background

We sought to determine the sites of recurrence and identify predicting factors for recurrence and survival in patients who underwent gastrectomy for adenocarcinoma at an institution where preoperative therapy is commonly used for advanced gastric cancer.

Methods

We collected clinicopathologic data and sites of recurrence from a prospectively maintained database of patients who underwent potentially curative resection of gastric or gastroesophageal adenocarcinoma at our institution in 1995–2014, and we assessed associations between these characteristics and recurrence patterns and survival.

Results

We identified 488 patients who underwent R0 resection of localized gastric cancer. The median age was 63 years (interquartile range 53–71 years), and 60% were male. The most common T and N categories, per endoscopic ultrasonography, were T3 (58%) and N0 (61%). Preoperative treatment was used in 61% of patients. A total of 125 (26%) patients experienced recurrence during follow-up. Recurrences were locoregional in 19 patients (15%), peritoneal in 61 (49%), and nonperitoneal distant in 67 (54%). The peritoneum also was the most common organ of recurrence (49%), followed by the liver (21%). The median time from primary resection to recurrence was 2.7 years for locoregional, 1.3 years for peritoneal, and 0.6 years for nonperitoneal distant recurrence (p = 0.01). Median overall survival was markedly shorter after peritoneal and nonperitoneal distant recurrences than after locoregional recurrences.

Conclusions

The peritoneum was a common site of recurrence after curative resection of gastric cancer and was associated with poor survival. Prophylactic treatment targeting the peritoneal cavity might improve survival of advanced gastric cancer.

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Lack of Efficacy of Radioiodine Remnant Ablation for Papillary Thyroid Microcarcinoma: Verification Using Inverse Probability of Treatment Weighting

Abstract

Background

Most of the increase in thyroid cancer in recent decades has been due to papillary thyroid microcarcinoma (PTMC). We evaluated the efficacy of radioiodine remnant ablation (RRA) in patients with PTMC.

Methods

This historical cohort study included 1932 PTMC patients without lateral cervical lymph node (LN) or distant metastasis who underwent total thyroidectomy (TT) during the median 8.3 years of follow-up. The clinical outcomes of patients with or without RRA were compared using weighted logistic regression models with the inverse probability of treatment weighting (IPTW) method and considering risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality, and central cervical LN metastasis.

Results

The median primary tumor size of the RRA group was significantly larger than that of the no-RRA group (0.7 vs. 0.5 cm, P < 0.001). There were significantly more patients with multifocality, extrathyroidal extension, and cervical LN metastasis in the RRA group compared with the no-RRA group. There was no significant difference in recurrence-free survival between the two groups (P = 0.11). Cox proportional–hazard analysis with IPTW by adjusting for clinicopathological risk factors demonstrated no significant difference in recurrence of PTMC according to RRA treatment (hazard ratio [HR] 2.02; 95% confidence interval [CI] 0.65–6.25; P = 0.2).

Conclusions

RRA had no therapeutic effect on the clinical outcomes of patients with PTMC who underwent TT. Surgical treatment without RRA could be applicable for patients with PTMC if there is no evidence of lateral cervical LN metastasis or distant metastasis.

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Refining the Role of Lymph Node Biopsy in Survival for Patients with Nasopharyngeal Carcinoma: Population-Based Study from the Surveillance Epidemiology and End-Results Registry

Abstract

Background

The updated version of the National Comprehensive Cancer Network (NCCN) guidelines revised pretreatment workup for nasopharyngeal carcinoma (NPC) into "biopsy of the primary site or neck." Despite provision of important diagnostic information, concerns regarding tumor cell dissemination limit the application of lymph node biopsy. This study aimed to investigate whether biopsy of the neck is associated with impaired survival in NPC.

Methods

A propensity score-matched, population-based cohort identified from the Surveillance, Epidemiology, and End Results database was used to compare overall survival (OS) and disease-specific survival (DSS) of patients who underwent pretreatment cervical lymph node biopsy without subsequent neck dissection or removal of node compared with patients who did not undergo node biopsy.

Results

Of 2910 eligible patients, 416 (14.3%) underwent pretreatment lymph node biopsy. After use of control for patient, tumor, and demographic characteristics, biopsy was not associated with impaired OS (hazard ratio [HR], 1.15; 95% confidence interval [CI] 0.89–1.47; P = 0.29) or DSS (HR, 1.07; 95% CI 0.81–1.40; P = 0.63). Interestingly, in the subgroup analysis, the unfavorable effect of biopsy was observed for patients with differentiated non-keratinizing squamous cell carcinoma (but not other histologic types). Race did not positively alter the survival outcomes.

Conclusions

The findings provide reference for clinical practice, showing that pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, except for patients with differentiated non-keratinizing squamous cell carcinoma. The recommended NCCN guidelines would be more specific by adding details to the general recommendation that neck biopsy is safe for all patients. Future prospective studies are needed to verify the study findings.

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Bilateral Prophylactic Mastectomy and Immediate Breast Reconstruction in High-Risk Women: The Importance of Health-Related Quality of Life in Decision Making

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$4M Verdict Smacks RJR, Found Responsible for Smoker's Throat Cancer Death - CVN News (blog)

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$4M Verdict Smacks RJR, Found Responsible for Smoker's Throat Cancer Death
CVN News (blog)
Hohnbaum also challenged the connection between Thomas' smoking and his cancer, noting a discrepancies in both Bertie Thomas' story and medical records, concerning whether Thomas had tongue cancer or laryngeal cancer. Pointing to medical ...

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Push to raise head and neck cancer awareness - Riverine Herald

Push to raise head and neck cancer awareness
Riverine Herald
An estimated five thousand Australians will be diagnosed with head or neck cancer this year, prompting a push to raise a awareness of the signs and symptoms. Cancer Council Australia is also encouraging teens to get the human papilloma virus ...

and more »

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Telomere shortening, TP53 mutations and deletions in chronic lymphocytic leukemia result in increased chromosomal instability and breakpoint clustering in heterochromatic regions

Abstract

Complex karyotypes are associated with a poor prognosis in chronic lymphocytic leukemia (CLL). Using mFISH, iFISH, and T/C-FISH, we thoroughly characterized 59 CLL patients regarding parameters known to be involved in chromosomal instability: status of the genes ATM and TP53 and telomere length. Interestingly, a deletion of the ATM locus in 11q, independent of the cytogenetic context, was associated with significantly diminished risk (p<0.05) of carrying a mutation in TP53. In patients with loss or mutation of TP53, chromosomal breakage occurred more frequently (p<0.01) in (near-) heterochromatic regions. Median telomere length in patients with complex karyotypes was significantly shorter than that of healthy controls and shorter than in all other cytogenetic cohorts. Furthermore, the median telomere length of patients carrying a TP53 mutation was significantly shorter than without mutation. We conclude that telomere shortening in combination with loss of TP53 induces increased chromosomal instability with preferential involvement of (near-) heterochromatic regions.

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Palliative home care for patients with advanced haematological malignancies—a multicenter survey

Abstract

Patients with advanced haematological malignancies in non-curative settings suffer from complex physical symptoms and psychosocial distress, comparable to patients with solid tumour entities. Nevertheless, numerous problems at the interface between haematology and palliative home care have been described. From January 2011 until October 2014, we performed a retrospective, multicenter analysis of all patients with haematological malignancies (ICD 10: C81-C95) being treated by the respective specialized palliative home care (SAPV) team. Three SAPV teams were surveyed. Disease entity, physical symptoms, psychosocial distress, number of hospital admissions, therapeutic interventions and other items were analysed descriptively. Of 3,955 SAPV patients, 1.8% (n = 73) suffered from haematological malignancies. Main problems were deterioration of general condition, pain or psychological problems. Thirty-seven percent developed new symptoms during SAPV, mainly pain, psychological distress or deterioration of general status. In 33%, patients were referred to hospital, mainly due to deterioration of general condition or pain. Seventy percent died within 3 months after beginning SAPV care; 83% died at home or in a nursing home. Patients suffering from advanced haematological malignancies were statistically underrepresented in SAPV, and SAPV was installed rather at the very last days of life. By far, more patients were able to die outside a hospital as compared to reference cohorts of haematological patients not being treated in SAPV. The spectrum of documented problems is comparable to other patient cohorts being treated in SAPV; therefore, the options and benefits of palliative home care should be incorporated in palliative haematological treatment concepts more vigorously and consequently.

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Interim 18 F-FGD PET/CT may not predict the outcome in primary central nervous system lymphoma patients treated with sequential treatment with methotrexate and cytarabine

Abstract

¹⁸F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17–75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.

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Advanced chronic myelomonocytic leukemia in elderly and frail patients managed by azacitidine in the field of clinical practice

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Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB in chronic or blast phase

Abstract

We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20–80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10⁹/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0–13). Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3–34) and 19 months (range 7–110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1–135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia, (c) presentation in chronic or blast phase, (d) rapid responses and long-term remission on low-dose imatinib, and (e) possible adverse prognostic impact of a complex karyotype.

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p38 MAPK Inhibits Nonsense-mediated RNA Decay in Response to Persistent DNA Damage in Non-cycling Cells [Gene Regulation]

Persistent DNA damage induces profound alterations in gene expression, which in turn influence tissue homeostasis, tumorigenesis, and cancer treatment outcome. However, the underlying mechanism for the gene expression reprogramming induced by persistent DNA damage remains poorly understood. Here, using a highly effective bioluminescence-based reporter system and other tools, we report that persistent DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, in noncycling cells. NMD suppression by persistent DNA damage required the activity of the p38α MAPK. Activating transcription factor 3 (ATF3), an NMD target and a key stress-inducible transcription factor, was stabilized in a p38α- and NMD-dependent manner following persistent DNA damage. Our results reveal a novel p38α-dependent pathway that regulates NMD activity in response to persistent DNA damage, which in turn controls ATF3 expression in affected cells.

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FDA Approves New Targeted Agent for Acute Myeloid Leukemia

The FDA has approved enasidenib (Idhifa) for the treatment of relapsed or refractory IDH2-mutant acute myeloid leukemia. (Source: CancerNetwork)

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Second-Line Therapy Options in Metastatic Renal Cell Carcinoma

This video reviews the various treatment options for metastatic renal cell carcinoma in the second-line setting, including considerations for different toxicity profiles. (Source: CancerNetwork)

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Betamethasone gel compared with lidocaine jelly to reduce tracheal tube related postoperative airway symptoms: a randomized controlled trial

Post-operative airway symptoms can be troublesome to patients following an uneventful general anesthesia with endotracheal intubation. In this study, we compared the effectiveness of lubricating an endotrachea...

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Does weight lifting improve visual acuity? A replication of Gonzalo-Fonrodona and Porras (2013)

A physical effort such as lifting up a weight affects our perception and cognition. A previous study reported in two experiments that weight lifting improves visual acuity. In the previous study, participants'...

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Magnitude and associated factors of anemia among pregnant women in Dera District: a cross-sectional study in northwest Ethiopia

Anemia is associated with adverse health and socio-economic consequences among pregnant women. Particularly, severe anemia increases the risk of maternal mortality by 20%. However, literatures are scarce in th...

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Effects of date palm pollen on fertility: research proposal for a systematic review

Over 10–15% of couples in different countries are infertile. Male infertility is a contributing factor and the only cause of infertility in respectively 50% and 20–30% of all cases of infertility. According to...

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Mitochondrial superoxide increases age-associated susceptibility of human dermal fibroblasts to radiation and chemotherapy

Elderly cancer patients treated with ionizing radiation (IR) or chemotherapy experience more frequent and greater normal tissue toxicity relative to younger patients. The current study demonstrates that exponentially growing fibroblasts from elderly (old) male donor subjects (70, 72, 78 years) are significantly more sensitive to clonogenic killing mediated by platinum-based chemotherapy and IR, (~70-80% killing) relative to young fibroblasts (5 months and 1 year; ~10-20% killing) and adult fibroblasts (20 years old; ~10-30% killing). Old fibroblasts also displayed significantly increased (2-4 fold) steady-state levels of O2·-, O2 consumption, and mitochondrial membrane potential as well as significantly decreased (40-50%) electron transport chain (ETC) complex I, II, IV, V, and aconitase (70%) activities, decreased ATP levels, and significantly altered mitochondrial structure. Following adenoviral-mediated overexpression of SOD2 activity (5-7 fold), mitochondrial ETC activity and aconitase activity were restored, demonstrating a role for mitochondrial O2·- in these effects. Old fibroblasts also demonstrated elevated levels of endogenous DNA damage that were increased following treatment with IR and chemotherapy. Most importantly, treatment with the small-molecule, superoxide dismutase (SOD) mimetic (GC4419; 0.25 µM), significantly mitigated the increased sensitivity of old fibroblasts to IR and chemotherapy and partially restored mitochondrial function without affecting IR or chemotherapy-induced cancer cell killing. These results support the hypothesis that age-associated increased O2·- and resulting DNA damage mediate the increased susceptibility of old fibroblasts to IR and chemotherapy and can be mitigated by GC4419.

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E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid [Research]

Tumor cell extravasation is a multistep process preceded by cell rolling and arrest on the vessel wall via the formation of specific receptor–ligand bonds. The strength, availability, and number of receptor–ligand bonds regulate the rate by which tumor cells tether, roll, and adhere to vascular walls. Although the mechanics of selectin-mediated rolling have been extensively studied, little is known regarding how tumor cell rolling on selectins facilitates adhesion to a distinct substrate-bound protein with different kinetic properties. By using multicomponent protein patterning and a microfluidic system, we evaluated how E-selectin-dependent rolling modulates hyaluronic acid (HA) adhesion as a function of fluid shear, contact time, and the spacing between E-selectin and HA regions patterned on the substrate. We show that tumor cells rolling on E-selectin were ~40-fold more likely to bind to HA than nonrolling cells in shear flow. Furthermore, E-selectin-dependent rolling promotes adhesion to HA by both physically slowing cells and enabling them to position proximal to the surface, thereby increasing the on rate of adhesion. A better understanding of tumor cell adhesion under physiologic shear would lead to the development of new diagnostic assays and pave the way to clinical approaches aimed ultimately to halt metastasis.—Shea, D. J., Li, Y. W., Stebe, K. J., Konstantopoulos, K. E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid.

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Prospective Evaluation of Multi-modal Optical Imaging with Automated Image Analysis to Detect Oral Neoplasia In Vivo

The five-year survival rate for patients with oral cancer remains low, in part because diagnosis often occurs at a late stage. Early and accurate identification of oral high-grade dysplasia and cancer can help improve patient outcomes. Multi-modal optical imaging is an adjunctive diagnostic technique in which autofluorescence imaging is used to identify high-risk regions within the oral cavity, followed by high resolution microendoscopy to confirm or rule out the presence of neoplasia. Multi-modal optical images were obtained from 206 sites in 100 patients. Histologic diagnosis, either from a punch biopsy or an excised surgical specimen, was used as the gold standard for all sites. Histopathologic diagnoses of moderate dysplasia or worse were considered neoplastic. Images from 92 sites in the first 30 patients were used as a training set to develop automated image analysis methods for identification of neoplasia. Diagnostic performance was evaluated prospectively using images from 114 sites in the remaining 70 patients as a test set. In the training set, multi-modal optical imaging with automated image analysis correctly classified 95% of non-neoplastic sites and 94% of neoplastic sites. Among the 56 sites in the test set that were biopsied, multi-modal optical imaging correctly classified 100% of non-neoplastic sites and 85% of neoplastic sites. Among the 58 sites in the test set that corresponded to a surgical specimen, multi-modal imaging correctly classified 100% of non-neoplastic sites and 61% of neoplastic sites. These findings support the potential of multi-modal optical imaging to aid in the early detection of oral cancer.

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Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States

Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The present analysis examined the effect of GTE consumption on liver injury in 1021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI) =3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI=2.5-5.1), which were significantly higher than those among women in the placebo arm (both P <0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an odds ratio of 7.0 (95% CI = 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations.

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Clinical Outcomes in pT4 Tongue Carcinoma are Worse than in pT3 Disease: How Extrinsic Muscle Invasion Should be Considered?

Abstract

Background

The identification of extrinsic tongue muscle invasion in oral cavity cancer remains challenging. Notably, the most recent American Joint Committee on Cancer (AJCC 2017, 8th edition) staging manual indicates that extrinsic muscle invasion does not lead to the diagnosis of a T4 tumor. Because this approach carries the risk of tumor downstaging, we compared the clinical outcomes of patients with oral tongue squamous cell carcinoma (SCC) staged as pT3 vs. pT4 according to the AJCC 2010, 7th edition criteria.

Methods

We retrospectively examined the records of consecutive patients with pT3 (n = 135) and pT4 (n = 68) tongue SCC who underwent radical surgery. Of the 68 pT4 tongue SCC, 63 (93%) had extrinsic muscle involvement alone. The 5-year locoregional control (LRC), distant metastasis (DM), and disease-free survival (DFS) rates served as outcome measures.

Results

Compared with pT3 tongue SCC, pT4 patients presented significantly more frequently with pN2 disease, extranodal extension, poor tumor differentiation, tumor depth >15 and >20 mm, margin status ≤4 mm, perineural invasion, vascular invasion, and were more frequently treated with surgery plus concurrent chemoradiotherapy. Less favorable 5-year outcomes were observed in patients with pT4 than pT3 tumors (LRC 50 vs. 75%, p < 0.001; DM 27 vs. 14%, p = 0.013; DFS 43 vs. 69%, respectively, p < 0.001). We identified pT4 disease (vs. pT3) as an independent adverse prognostic factor for LRC and DFS.

Conclusions

We suggest classifying patients with tongue SCC and extrinsic muscle invasion as having pT4 disease.

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Radical Lymph Node Dissection Along the Proximal Splenic Artery During Laparoscopic Gastrectomy for Gastric Cancer Using the Left Lateral Approach

Abstract

Background

Recent technical improvements allow safe laparoscopic lymph node dissection (LND) in gastric cancer.1 ^,2 In suprapancreatic LND, careful LND around the celiac artery (CA) is essential. From a patient's right side, deep LND is performed around the right side of the CA after dissecting around the common hepatic artery (CHA). For LND around the left side of the CA on the same operative axis as the right side, we developed a new procedure for LND along the proximal splenic artery (SA), performed from the patient's left side.

Methods

After LND around the CHA and right side of the CA from the patient's right side, the surgeon then moves to the patient's left side. The anterior pancreatic fascia is cut at the middle point of the SA to discern the dorsal layer of the LN along the SA, such as the splenic vein. LND is performed by preserving the posterior pancreatic fascia around the SA in a left-to-right direction. Finally, the LNs around the left side of the CA are deeply dissected.

Results

We performed this procedure on ten patients between April 2016 and January 2017; no operative complications were reported in grade II or higher cancer patients.3 After exposing the dorsal landmark, LNs around the proximal SA and left side of the CA were removed in all patients.

Conclusion

This procedure enables early identification of the dorsal layer and deep LND around the left side of the CA, keeping this layer. The left lateral approach is useful for radical LND along the proximal SA.

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Pertuzumab/Trastuzumab/CT Versus Trastuzumab/CT Therapy for HER2+ Breast Cancer: Results from the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

Abstract

Background

Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping.

Methods

Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S. institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted therapy and underwent surgery. This study compared the pathologic complete response (pCR) rate of BluePrint versus clinical subtypes with treatment, specifically differences between trastuzumab (T) treatment and trastuzumab and pertuzumab (T/P) treatment.

Results

In this study, 60% of the patients received NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%. BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This was significantly higher than the pCR rate for the 91 HER2+ tumors (31%) classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than those treated with trastuzumab alone. The difference was most pronounced in the BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the BluePrint HER2-type patients treated with T/P (76%).

Conclusions

The addition of pertuzumab leads to increased pCR rates for all HER2+ patient groups except for the BluePrint basal-type patients. This better response was most pronounced for the BluePrint luminal-type patients.

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Sentinel Lymph Node Biopsy for Recurrent Melanoma: A Multicenter Study

Abstract

Background

Sentinel lymph node biopsy (SLNB) is routinely performed for primary cutaneous melanomas; however, limited data exist for SLNB after locally recurrent (LR) or in-transit (IT) melanoma.

Methods

Data from three centers performing SLNB for LR/IT melanoma (1997 to the present) were reviewed, with the aim of assessing (1) success rate; (2) SLNB positivity; and (3) prognostic value of SLNB in this population.

Results

The study cohort included 107 patients. Management of the primary melanoma included prior SLNB for 56 patients (52%), of whom 10 (18%) were positive and 12 had complete lymph node dissections (CLNDs). In the present study, SLNB was performed for IT disease (48/107, 45%) or LR melanoma (59/107, 55%). A sentinel lymph node (SLN) was removed in 96% (103/107) of cases. Nodes were not removed for four patients due to lymphoscintigraphy failures (2) or nodes not found during surgery (2). SLNB was positive in 41 patients (40%, 95% confidence interval (CI) 31.5–50.5), of whom 35 (88%) had CLND, with 13 (37%) having positive nonsentinel nodes. Median time to disease progression after LR/IT metastasis was 1.4 years (95% CI 0.75–2.0) for patients with a positive SLNB, and 5.9 years (95% CI 1.7–10.2) in SLNB-negative patients (p = 0.18). There was a trend towards improved overall survival for patients with a negative SLNB (p = 0.06).

Conclusion

SLNB can be successful in patients with LR/IT melanoma, even if prior SLNB was performed. In this population, the rates of SLNB positivity and nonsentinel node metastases were 40% and 37%, respectively. SLNB may guide management and prognosis after LR/IT disease.

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Cosmetic Outcome and Chronic Breast Toxicity After Intraoperative Radiation Therapy (IORT) as a Single Modality or as a Boost Using the Intrabeam ® Device: A Prospective Study

Abstract

Purpose

We aim to report our results in terms of chronic toxicities and cosmetic outcomes after intraoperative radiotherapy (IORT) using kV X-rays in women treated for early breast cancer at our institution.

Methods

Patients with early breast carcinoma were recruited between April 2011 and November 2014. After breast-conserving surgery, patients were treated with IORT using the Intrabeam^® device. IORT was completed by whole-breast radiotherapy (WBRT) at a dose of 46–50.4 Gy in 23–28 fractions in case of adverse pathologic criteria on the final specimen examination. Skin toxicity was graded using the Late Effects in Normal Tissues—Subjective, Objective, Management and Analytic (LENT-SOMA) scale every 6 months, and cosmetic outcomes were evaluated at 36 months by patient self-evaluation and by two radiation oncologists, on a 1–10 scale.

Results

Forty-one women received IORT only and 30 patients received IORT followed by WBRT (IORT + WBRT group). After a median follow-up of 38.9 months, no locoregional or distant recurrence occurred. After IORT only, 2.4% of grade 2 or higher breast fibrosis, and no other grade 2 or higher disease, was observed. In the IORT + WBRT group, grade 2 or higher fibrosis and grade 2 or higher breast retraction were observed in 43.3 and 23.3% of patients, respectively. Objective cosmetic outcomes were very good and significantly better in the IORT-only group compared with the IORT + WBRT group (8.87 vs. 6.96) (p < 0.001).

Conclusion

IORT using the Intrabeam^® is well-tolerated, with very little chronic toxicity and good cosmetic outcome. However, a high rate of grade 2 or higher chronic breast toxicity was observed when IORT had to be completed by WBRT.

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The Impact of Residual Disease After Preoperative Systemic Therapy on Clinical Outcomes in Patients with Inflammatory Breast Cancer

Abstract

Background

Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients.

Methods

Following review of IBC patients' records (1997–2014), we identified 258 stage III IBC patients; 181 received PST followed by MRM and radiotherapy and were subsequently analyzed. Pathologic complete response (pCR) to PST, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, grade, and histology were evaluated as predictors of TTR and OS by Cox model.

Results

Overall, 95/181 (52%) patients experienced recurrence; 93/95 (98%) were distant metastases (median TTR 3.2 years). Seventy-three patients (40%) died (median OS 6.9 years). pCR was associated with improved TTR (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09–0.46, p < 0.01, univariate; HR 0.17, 95% CI 0.07–0.41, p < 0.0001, multivariate) and improved OS (HR 0.26, 95% CI 0.11–0.65, p < 0.01, univariate). In patients with pCR, grade III (HR 1.91, 95% CI 1.16–3.13, p = 0.01), and triple-negative phenotype (HR 3.54, 95% CI 1.79–6.98, p = 0.0003) were associated with shorter TTR, while residual ductal carcinoma in situ was not (HR 0.85, 95% CI 0.53–1.35, p = 0.48, multivariate).

Conclusions

In stage III IBC, pCR was associated with prognosis, further influenced by grade, hormone receptor, and HER2 status. Investigating mechanisms that contribute to better response to PST could help improve oncologic outcomes in IBC.

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Analysis of Perioperative Chemotherapy in Resected Pancreatic Cancer: Identifying the Number and Sequence of Chemotherapy Cycles Needed to Optimize Survival

Abstract

Purpose

Receipt of 6 cycles of adjuvant chemotherapy (AC) is standard of care in pancreatic cancer (PC). Neoadjuvant chemotherapy (NAC) is increasingly utilized; however, optimal number of cycles needed alone or in combination with AC remains unknown. We sought to determine the optimal number and sequence of perioperative chemotherapy cycles in PC.

Methods

Single institutional review of all resected PCs from 2008 to 2015. The impact of cumulative number of chemotherapy cycles received (0, 1–5, and ≥6 cycles) and their sequence (NAC, AC, or NAC + AC) on overall survival was evaluated Cox-proportional hazard modeling, using 6 cycles of AC as reference.

Results

A total of 522 patients were analyzed. Based on sample size distribution, four combinations were evaluated: 0 cycles = 12.1%, 1–5 cycles of combined NAC + AC = 29%, 6 cycles of AC = 25%, and ≥6 cycles of combined NAC + AC = 34%, with corresponding survival. 13.1, 18.5, 37, and 36.8 months. On MVA (P < 0.0001), tumor stage [hazard ratio (HR) 1.35], LNR (HR 4.3), and R1 margins (HR 1.77) were associated with increased hazard of death. Compared with 6 cycles AC, receipt of 0 cycles [HR 3.57, confidence interval (CI) 2.47–5.18] or 1–5 cycles in any combination (HR 2.37, CI 1.73–3.23) was associated with increased hazard of death, whereas receipt of ≥6 cycles in any sequence was associated with optimal and comparable survival (HR 1.07, CI 0.78–1.47).

Conclusions

Receipt of 6 or more perioperative cycles of chemotherapy either as combined neoadjuvant and adjuvant or adjuvant alone may be associated with optimal and comparable survival in resected PC.

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Immaturity of Bile Canalicular–Ductule Networks in the Future Liver Remnant While Associating Liver Partition and Portal Vein Occlusion for Staged Hepatectomy (ALPPS)

Abstract

Background

We studied histologic changes of bile canalicular–ductule networks in the future liver remnant (FLR) while associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS), since little is known about regeneration of these networks during the relatively short interval between procedures in ALPPS.

Methods

Bile canalicular–ductule networks were examined in specimens from eight patients treated with ALPPS and six patients undergoing hepatectomy following portal vein embolization (PVE). Expression of multidrug resistance-1 (MDR1), a membrane transporter in bile canaliculi (BC), was analyzed immunohistochemistcally. Morphologic changes of BC and tight junctions (TJs) adjoining BC were also assessed electron microscopically.

Results

Extrapolated kinetic growth of the FLR was greater during ALPPS (17.2 ± 6.8 mL/day) than after PVE (6.3 ± 3.4 mL/day; p = 0.005), and continuity of the MDR1-positive bile canalicular networks was less evident in ALPPS than PVE (p < 0.001). Electron microscopically, no significant difference was evident in numbers of BC or BC lumen size between the two groups; however, development of microvilli in BC was poorer in the ALPPS group than in the PVE group (p < 0.001). TJ/desmosome complexes were shorter in the ALPPS group (0.69 ± 0.52 μm) than in the PVE group (1.09 ± 0.50 μm; p < 0.001), and leaky TJs were seen more frequently in the ALPPS group (64.9 vs. 23.6%; p = 0.001).

Conclusions

Regeneration of bile canalicular–ductule networks in the FLR was poorer in ALPPS than PVE, which may be associated with prolonged cholestasis following final hepatectomy in ALPPS.

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Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy

Abstract

Background

The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR).

Objective

The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC.

Methods

Patients with stage I–III ER+, HER2− breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP).

Results

From 2007 to 2016, 402 ER+/HER2− cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II–III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p < 0.0001). Patients with ILC initially ineligible for BCS (n = 56) were less likely to downstage than those with invasive ductal carcinoma (IDC; n = 183, 16 vs. 48%, p ≤ 0.0001), with a similar trend in the axilla (p = 0.086). The rates of BCS eligibility after NAC were highest in PR−/HP patients (62%) and lowest in PR+/non-HP patients (29%) [p = 0.005]. In the axilla, nodal pCR among cN+ patients (n = 301) ranged from 0 to 35% (p < 0.0001) within these groups, and was most frequent in PR−/HP patients.

Conclusions

ER+/HER2− patients most likely to benefit from NAC are those with PR− and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.

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Αρχειοθήκη ιστολογίου

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Τρίτη 1 Αυγούστου 2017

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