Total iron-binding capacity is a novel prognostic marker after curative gastrectomy for gastric cancer

Abstract

Background

Patients with gastric cancer (GC) are affected by changes in iron status. Before surgery, GC patients are likely to have iron-deficiency anemia; and after gastrectomy, patients suffer from low nutritional status and low iron. This study investigated preoperative iron status associated with prognosis after curative gastrectomy for gastric cancer.

Methods

We evaluated preoperative serum hemoglobin (Hgb), Fe and total iron-binding capacity (TIBC) in 298 patients who underwent curative gastrectomy for GC without preoperative chemotherapy, and analyzed these factors' associations with prognosis after surgery.

Results

Of the 298 patients, 129 (43.2%) had low Hgb levels, and 33 (11.1%) had low TIBC (< 260 µg/dl) that was not associated with Hgb or Fe level. Patients with low TIBC were significantly associated with older age (≥ 65 years old; P = 0.0085), low albumin (< 3.9 g/dl; P = 0.0388) and high CRP (≥ 0.15 mg/dl; P = 0.0018) in multivariate analysis. Low Fe (< 60 µg/dl) was not associated with disease-free survival (DFS) or overall survival (OS); however, low Fe was associated with longer cancer-specific survival in Stage III GC patients (P = 0.0333). Both low Hgb and low TIBC were significantly associated with shorter DFS (Hgb: P = 0.0433; TIBC: P < 0.0001) and shorter OS (Hgb: P = 0.0352; TIBC: P < 0.0001). Low TIBC were significantly associated with shorter DFS (HR 2.167, 95% CI 1.231–3.639, P = 0.0086) and shorter OS (HR 2.065, 95% CI 1.144–3.570, P = 0.0173) in multivariate Cox hazard regression analysis.

Conclusions

Preoperative serum TIBC level of GC patients who undergo curative gastrectomy is a novel prognostic marker in univariate and multivariate analyses.

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Patient-Reported Outcomes After ADM Breast Reconstruction

How do patients feel after undergoing ADM-assisted implant-based breast reconstruction? Are they generally satisfied with the outcomes?
Plastic Reconstructive Surgery-Global Open (PRS Global Open)

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20Q: Effective Counseling = Information + Feelings

This article is written in an engaging Q & A style and discusses relevant counseling principles and tools from psychology that may help audiologists facilitate positive patient outcomes.

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Cortical processing of speech in individuals with auditory neuropathy spectrum disorder

Abstract

Objective

Auditory neuropathy spectrum disorder (ANSD) is a condition where cochlear amplification function (involving outer hair cells) is normal but neural conduction in the auditory pathway is disordered. This study was done to investigate the cortical representation of speech in individuals with ANSD and to compare it with the individuals with normal hearing.

Design

Forty-five participants including 21 individuals with ANSD and 24 individuals with normal hearing were considered for the study. Individuals with ANSD had hearing thresholds ranging from normal hearing to moderate hearing loss. Auditory cortical evoked potentials—through odd ball paradigm—were recorded using 64 electrodes placed on the scalp for /ba/-/da/ stimulus. Onset cortical responses were also recorded in repetitive paradigm using /da/ stimuli. Sensitivity and reaction time required to identify the oddball stimuli were also obtained.

Result

Behavioural results indicated that individuals in ANSD group had significantly lower sensitivity and longer reaction times compared to individuals with normal hearing sensitivity. Reliable P300 could be elicited in both the groups. However, a significant difference in scalp topographies was observed between the two groups in both repetitive and oddball paradigms. Source localization using local auto regressive analyses revealed that activations were more diffuses in individuals with ANSD when compared to individuals with normal hearing sensitivity.

Conclusion

Results indicated that the brain networks and regions activated in individuals with ANSD during detection and discrimination of speech sounds are different from normal hearing individuals. In general, normal hearing individuals showed more focused activations while in individuals with ANSD activations were diffused.

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Cortical processing of speech in individuals with auditory neuropathy spectrum disorder

Abstract

Objective

Auditory neuropathy spectrum disorder (ANSD) is a condition where cochlear amplification function (involving outer hair cells) is normal but neural conduction in the auditory pathway is disordered. This study was done to investigate the cortical representation of speech in individuals with ANSD and to compare it with the individuals with normal hearing.

Design

Forty-five participants including 21 individuals with ANSD and 24 individuals with normal hearing were considered for the study. Individuals with ANSD had hearing thresholds ranging from normal hearing to moderate hearing loss. Auditory cortical evoked potentials—through odd ball paradigm—were recorded using 64 electrodes placed on the scalp for /ba/-/da/ stimulus. Onset cortical responses were also recorded in repetitive paradigm using /da/ stimuli. Sensitivity and reaction time required to identify the oddball stimuli were also obtained.

Result

Behavioural results indicated that individuals in ANSD group had significantly lower sensitivity and longer reaction times compared to individuals with normal hearing sensitivity. Reliable P300 could be elicited in both the groups. However, a significant difference in scalp topographies was observed between the two groups in both repetitive and oddball paradigms. Source localization using local auto regressive analyses revealed that activations were more diffuses in individuals with ANSD when compared to individuals with normal hearing sensitivity.

Conclusion

Results indicated that the brain networks and regions activated in individuals with ANSD during detection and discrimination of speech sounds are different from normal hearing individuals. In general, normal hearing individuals showed more focused activations while in individuals with ANSD activations were diffused.

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Awareness of HPV and Cervical Cancer Prevention Among University Health Sciences Students in Cyprus

Abstract

Cervical cancer is preventable; however, despite the existence of primary and secondary means of prevention, its incidence is still higher in certain socioeconomic groups and countries, suggesting gaps in cervical cancer prevention. The objective of this study was to evaluate the knowledge and awareness of health sciences university students in Cyprus regarding HPV and cervical cancer in order to better guide the future development of educational programs to improve cervical cancer prevention. This was a cross-sectional study of 178 university health sciences students in Cyprus using a validated questionnaire on HPV and cervical cancer prevention. Analysis of the completed questionnaires revealed moderate levels of knowledge and awareness with an overall mean score of 23.32 out of 33 on HPV and 8.12 out of 13 on cervical cancer, a score of 9.25 out of 14 on HPV vaccines, and a score of 5.93 out of 9 on cervical cancer screening. Older students achieved higher scores compared to younger students (mean score of 6.76 for 18–22 years old, 9.44 for 23–28 years old, and 10.25 for 29–38 years old; p < 0.001). The study found several gaps in the students' knowledge and awareness on cervical cancer prevention. We suggest the design of education programs targeting this population possibly by incorporation of cervical cancer prevention education within students' curriculum to increase knowledge such that the spread of the virus is minimized and these health sciences students are prepared to educate their communities as part of their future practice in health professions.

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In-vitro and in-vivo design and validation of an injectable polysaccharide-hydroxyapatite composite material for sinus floor augmentation

Publication date: Available online 7 April 2018
Source:Dental Materials
Author(s): J.C. Fricain, R. Aid, S. Lanouar, D.B. Maurel, D. Le Nihouannen, S. Delmond, D. Letourneur, J. Amedee Vilamitjana, S. Catros
ObjectivePolysaccharide-based composite matrices consisting of natural polysaccharides, pullulan and dextran supplemented with hydroxyapatite (Matrix-HA) have recently been developed. The principal objective of this study was to evaluate the capacities of this composite material to promote new bone formation in a sinus lift model in the sheep. Secondary objectives were to evaluate in vitro properties of the material regarding cell adhesion and proliferation.MethodsIn this report, once such composite matrix was prepared as injectable beads after dispersion in a physiological buffer, and evaluated using a large animal model (sheep) for a sinus lift procedure.ResultsIn vitro studies revealed that these microbeads (250–550μm in diameter) allow vascular cell adhesion and proliferation of Endothelial Cells (EC) after 1 and 7 days of culture. In vivo studies were performed in 12 adult sheep, and newly formed tissue was analyzed by Cone Beam Computed Tomography (CBCT scanning electron microscopy (SEM) and by histology 3 and 6 months post-implantation. CBCT analyses at the implantation time revealed the radiolucent properties of these matrices. Quantitative analysis showed an increase of a dense mineralized tissue in the Matrix-HA group up to 3 months of implantation. The mineralized volume over total volume after 6 months reached comparable values to those obtained for Bio-Oss^® used as positive control. Histological examination confirmed that the Matrix-HA did not induce any long term inflammatory events, and promoted direct contact between the osteoid tissue and lamellar bone structures and beads. After 6 months, we observed a dense network of osteocytes surrounding both biomaterials as well as a newly vascularized formed tissue in close contact to the biomaterials.SignificanceIn conclusion, the absence of animal components in Matrix-HA, the osteoconductive property of Matrix-HA in sheep, resulting in a dense bone and vascularized tissue, and the initial radiolucent property to follow graft integration offer great promises of this composite material for clinical use.



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Three-dimensional evaluation of mandibular asymmetry: a new classification and three-dimensional cephalometric analysis

Publication date: Available online 8 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): M.Y. Leung, Y.Y. Leung
Mandibular asymmetry is common among orthognathic patients and exhibits great variation. The aim of this study was to propose a new classification of mandibular asymmetry by anatomical regions; namely R (ramus), B (mandibular body) and C (chin), in conjunction with a corresponding 'RBC' three-dimensional (3D) cephalometric analysis. The cone beam computed tomography data of 65 patients with mandibular asymmetry was retrieved to perform the RBC 3D cephalometric analysis and to investigate the characteristics of mandibular asymmetry. It was found that the more posteriorly in mandible, the more pronounced was the vertical asymmetry. Significant transverse asymmetry was only noted in mandibular body. Both mandibular body and chin were significantly asymmetric in length. Seven significant morphologic predictors of menton deviation were identified, namely lower dental midline shift, difference in ramus height, difference in chin length, difference in body length, body height on contralateral side, coronoid height on deviated side and body width on contralateral side, confirming the complex nature of mandibular asymmetry. This simple and concise classification allows comprehensive assessment of mandible morphology by anatomical regions which also facilitates diagnosis, treatment planning and communication in both clinical and research settings.



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A novel digital workflow to manufacture personalized three-dimensional-printed hollow surgical obturators after maxillectomy

Publication date: Available online 7 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): J. Kortes, H. Dehnad, A.N.T. Kotte, W.M.M. Fennis, A.J.W.P. Rosenberg
Partial or complete resection of the maxilla during tumour surgery causes oronasal defects, leading to oral-maxillofacial dysfunction, for which the surgical obturator (SO) is an important treatment option. Traditional manufacturing of SOs is complex, time-consuming, and often results in inadequate fit and function. This technical note describes a novel digital workflow to design and manufacture a three-dimensional (3D)-printed hollow SO. Registered computed tomography and magnetic resonance imaging images are used for gross tumour delineation. The produced RTStruct set is exported as a stereolitography (STL) file and merged with a 3D model of the dental status. Based on these merged files, a personalized and hollow digital SO design is created, and 3D printed. Due to the proper fit of the prefabricated SO, a soft silicone lining material can be used during surgery to adapt the prosthesis to the oronasal defect, instead of putty materials that are not suitable for this purpose. An STL file of this final SO is created during surgery, based on a scan of the relined SO. The digital workflow results in a SO weight reduction, an increased fit, an up-to-date digital SO copy, and overall easier clinical handling.



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Lewy Body Disease: Clinical and Pathological “Overlap Syndrome” Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease)

Abstract

Lewy body disease (LBD) is a neurodegenerative disease resulting in dementia. It shares clinical and pathological features with Parkinson disease (PD), the most frequent synucleinopathy, Parkinson disease dementia (PDD), and Alzheimer disease (AD), a tauopathy. Even though the diagnostic criteria for these neurodegenerative diseases are clearly established, and recently revised for LBD, their precise clinical diagnosis is often difficult because LBD, PD, PDD, and AD share epidemiological, clinical, and pathological characteristics. This manuscript discusses current understanding of overlapping symptoms and the particular features of LBD, PD, and AD. It also describes features that could facilitate the diagnosis of each of these diseases. We concluded that the concept of neurodegenerative "overlap" syndrome, which includes the accepted diagnosis of LBD, may be taken in account and should contribute to clarifying LBD and definitions of close differential diagnoses. This should allow clinicians to suspect LBD at an earlier stage and provide better patient care.

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DOES fixation METHOD EFFECTS temporomandibular joints after mandibular advancement?

Publication date: Available online 7 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Erdogan Utku Ureturk, Aysegul Apaydin
PurposeSagittal split ramus osteotomy (SSRO) is a standard procedure in which miniplates and screws are used to achieve stabilization. Although the titanium plate and screw fixation system is stable, resorbable fixation systems are also used. There is currently no consensus on the ideal fixation technique for SSRO procedures and its effect on the condyle. We aimed to evaluate the stress distribution on temporomandibular joints (TMJ).MethodsA 3D finite element model of a hemimandible was designed and 5 mm advancement was simulated on a computer model. Four different fixation techniques were applied: inverted-L shaped bicortical screws, L-shaped bicortical screws, miniplate with monocortical screws, and miniplate with monocortical screws and bicortical screw. Computer models were prepared twice for resorbable and titanium material. Load of 600N and muscle forces were applied. In the finite element analysis, computer models simulated and analyzed stress distribution of bone, fixation materials and condyle.ResultsBicortical screws increase the total stress on TMJ, and the stress is located more on the posterior part than the anterior. Miniplates decrease the stress, and the forces are located more on the anterior aspect of the TMJ.ConclusionAccording to our analysis, the use of bicortical screws increases the stress amount on the condyle. For the patients with a tendency toward temporomandibular disorders, using miniplate fixation techniques may decrease the forces around the condyle. These findings should be useful for oral surgeons when deciding on the most appropriate fixation technique in patients with a tendency toward temporomandibular joint disorders.



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DOES fixation METHOD EFFECTS temporomandibular joints after mandibular advancement?

Publication date: Available online 7 April 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Erdogan Utku Ureturk, Aysegul Apaydin
PurposeSagittal split ramus osteotomy (SSRO) is a standard procedure in which miniplates and screws are used to achieve stabilization. Although the titanium plate and screw fixation system is stable, resorbable fixation systems are also used. There is currently no consensus on the ideal fixation technique for SSRO procedures and its effect on the condyle. We aimed to evaluate the stress distribution on temporomandibular joints (TMJ).MethodsA 3D finite element model of a hemimandible was designed and 5 mm advancement was simulated on a computer model. Four different fixation techniques were applied: inverted-L shaped bicortical screws, L-shaped bicortical screws, miniplate with monocortical screws, and miniplate with monocortical screws and bicortical screw. Computer models were prepared twice for resorbable and titanium material. Load of 600N and muscle forces were applied. In the finite element analysis, computer models simulated and analyzed stress distribution of bone, fixation materials and condyle.ResultsBicortical screws increase the total stress on TMJ, and the stress is located more on the posterior part than the anterior. Miniplates decrease the stress, and the forces are located more on the anterior aspect of the TMJ.ConclusionAccording to our analysis, the use of bicortical screws increases the stress amount on the condyle. For the patients with a tendency toward temporomandibular disorders, using miniplate fixation techniques may decrease the forces around the condyle. These findings should be useful for oral surgeons when deciding on the most appropriate fixation technique in patients with a tendency toward temporomandibular joint disorders.



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Comparison of functional outcomes after total thyroidectomy and completion thyroidectomy: Hypoparathyroidism and postoperative complications

This study aimed to investigate differences in functional outcomes of postoperative complications and hypoparathyroidism between patients who underwent completion thyroidectomy (CT) after thyroid lobectomy or total thyroidectomy (TT) as an initial treatment.

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Surgical outcomes in the treatment of temporal bone cerebrospinal fluid leak: A systematic review

Temporal bone cerebrospinal fluid (CSF) leakage may have acquired or spontaneous origin. Acquired temporal bony defects typically comprise traumatic injuries, iatrogenic causes, chronic otitis media with or without cholesteatoma, irradiation, neoplastic invasion of the skull base [1]. Concerning the etiology of spontaneous temporal CSF leaks some authors suggest that small bony defects of the middle fossa tegmen originating from imperfect embryologic development may progressively expand with constant CSF pressure [2].

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Three-dimensional evaluation of mandibular asymmetry: a new classification and three-dimensional cephalometric analysis

Mandibular asymmetry is common among orthognathic patients and exhibits great variation. The aim of this study was to propose a new classification of mandibular asymmetry by anatomical regions; namely R (ramus), B (mandibular body) and C (chin), in conjunction with a corresponding 'RBC' three-dimensional (3D) cephalometric analysis. The cone beam computed tomography data of 65 patients with mandibular asymmetry was retrieved to perform the RBC 3D cephalometric analysis and to investigate the characteristics of mandibular asymmetry.

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Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis

Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews
Author(s): Dong Yeon Jeong, Sang Woo Lee, Young Ha Park, Ji Hoon Choi, Young Wook Kwon, Gabin Moon, Michael Eisenhut, Andreas Kronbichler, Jae Il Shin
Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease which results from the irreversible loss of self-tolerance and impaired molecular responses, especially an altered interferon signature. We synthesized all meta-analyses reporting a genetic association of SLE, and further investigated their validity to discover false positive results under Bayesian methods. We executed a PubMed search to extract the respective results regarding gene polymorphisms of SLE, published until June 30th 2017 and selected a single result per genetic variant among duplicates. Among 133 significant genotype comparisons, 45 (34%) were found noteworthy under both false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). From the meta-analysis of genome-wide association studies (GWAS), we could confirm that all significant comparisons were noteworthy under both Bayesian approaches. Both approaches may be advantageous for determining whether the reported associations is genuine, especially for interpreting results from observational studies instead of GWAS whose significance was determined in a more strict manner. When determining results from GWAS with a p-value ranging between 0.05 and 5 × 10⁻⁸, other statistical approaches, rather than single standard significance may be beneficial. Taking into account these considerations, a proportion of meta-analyses claimed statistical significance, but these results need to be interpreted with caution.



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Should rheumatoid factor (RF) (and antinuclear antibodies (ANA)) become routinary screening test for morbidities in the general population?

Publication date: Available online 8 April 2018
Source:Autoimmunity Reviews
Author(s): Gianfranco Ferraccioli, Stefano Alivernini, Barbara Tolusso, Elisa Gremese




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EMCrit RACC Podcast 222 / EDECMO Podcast – Demetris Yannopoulos on ECPR-the Minneapolis Way

Yannopoulos on ECPR

EMCrit Project by Scott Weingart.

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Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in Scotchwoman: the chosen clone matters—reply

Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): Dai-Zhong Wang, Li Yao, Xian-Bin Tang




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The clinicopathological significance of micropapillary pattern in colorectal cancers

Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): Jung-Soo Pyo, Mee Ja Park, Dong-Wook Kang
The aim of the present study is to elucidate the clinicopathological significance and prognostic role of micropapillary pattern (MPP) in colorectal cancer (CRC). We investigated the correlation between the presence of MPP and clinicopathological characteristics and prognosis in 266 CRCs. In addition, the clinicopathological significance of MPP in mucin pools was investigated and compared to pure MPP, which is not associated with mucin pools. MPP, regardless of its proportion in the overall tumor, was found in 74 of 266 CRCs (27.8%). The rate of MPP in proportions ≥5% was 9.4% (25 of 266 cases). CRC with MPP showed higher rates of vascular and lymphatic invasion, higher metastatic lymph node ratio, and higher pT stage compared to CRC without MPP. In addition, increasing proportion of MPP in overall tumor showed more frequent vascular and lymphatic invasions (P=.002 and P=.008, respectively). Among 74 CRCs with MPP, 25 CRCs were found in mucin pools (33.8%). These cases were more right-sided and poorly differentiated with less frequent lymphatic invasion and lymph node metastasis, compared to CRCs with pure MPP. The presence of MPP significantly correlated with worse overall survival (P=.010). In 74 CRCs with MPP, overall survival significantly differed between pure MPP and MPP in mucin pools (P=.003). Taken together, our data suggest that the presence of MPP significantly correlated with aggressive tumor behavior and worse survival in CRC. In addition, the clinicopathological significance of MPP in mucin pools differed from CRC with pure MPP.



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MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma

Publication date: Available online 8 April 2018
Source:Human Pathology
Author(s): Meng Zhang, Guichao Li, Xiangjie Sun, Shujuan Ni, Cong Tan, Midie Xu, Dan Huang, Fei Ren, Dawei Li, Ping Wei, Xiang Du
MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma.



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Clinical implication of programmed death-ligand 1 expression in tonsillar squamous cell carcinoma in association with intratumoral heterogeneity, human papillomavirus, and epithelial-to-mesenchymal transition

Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): Mi Jung Kwon, Young-Soo Rho, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Eun Soo Kim, Bumjung Park, Mineui Hong, Kyueng-Whan Min
Programmed death-ligand 1 (PD-L1), essential for immune evasion, is a potential candidate for pathogenesis and therapeutic target of human papillomavirus (HPV)-positive tonsillar squamous cell carcinomas (TSCCs). MET/hepatocyte growth factor (HGF) signaling and transcription factors involved in epithelial-to-mesenchymal transition (EMT) upregulate PD-L1, which can contribute to clinical outcome. Intratumoral heterogeneity of PD-L1 expression is of clinical importance in selection bias due to false-negative patient enrollment. However, the clinicopathological features, prognostic value, and co-expressed molecules of PD-L1 remain unclear in TSCCs. PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP142) between whole tissue and tissue microarray (TMA) sections of 79 tumors (5% cutoff value with weak staining). Expressions of EMT markers (TWIST1, Snail, and SNIP1) and MET/HGF were also analyzed. Staining of the TMA sections showed 78.5% concordance rate to the whole section. PD-L1 positivity and its intratumoral heterogeneity were 29.1% and 15.2% of TSCCs by whole section, respectively. PD-L1 positivity was prevalent in females, HPV-positive tumors without base of tongue invasion, and SNIP1-overexpressed tumors. SNIP1 overexpression, unmethylated TWIST1, smoking, and poorly-differentiated tumors were predictive for PD-L1 overexpression. PD-L1 positivity was a favorable independent prognostic factor. Subgroup analyses according to the co-expression of PD-L1 with HPV, SNIP1, or unmethylated TWIST1 indicated the best clinical outcome than any other subgroups. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequent, warranting a caution in punching TMA cores. A combined analysis of PD-L1 with EMT and HPV may define a characteristic subset of patients and prognostic group.



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Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in schwannomas: the chosen clone matters

Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): David Creytens, Mieke Van Bockstal, Liesbeth Ferdinande, Jo Van Dorpe




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Endoscope-assisted nasal dermoid excision with an open rhinoplasty approach

Publication date: June 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 109
Author(s): Devon M. Livingstone, James Brookes, Warren K. Yunker
Congenital midline nasal masses have been traditionally excised through rhinotomies and bicoronal incisions. These approaches are disfiguring and potentially morbid, leading pediatric otolaryngologists to seek out less invasive, endoscopic-assisted approaches. Here we present a nasal dermoid excised with a minimally invasive, endoscopic assisted open rhinoplasty approach. The preoperative workup as well as perioperative steps for excision are documented, with the hope that this will assist other practitioners with this approach. An endoscopic open rhinoplasty technique affords excellent visualisation, with a superior cosmetic outcome. A preoperative MRI is essential to ensure the lesion is amenable to this approach.



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Re “Calcification of Thoracic and Abdominal Aneurysms is Associated with Mortality and Morbidity”. Abdominal Aortic Aneurysm Calcification: Are Biochemical Markers a Missing Piece of the Puzzle?

Publication date: Available online 7 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Emirena Garrafa, Stefano Bonardelli




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Clinical Effect and Cost-Effectiveness of Screening for Asymptomatic Carotid Stenosis: A Markov Model

Publication date: Available online 7 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Dominika Högberg, Kevin Mani, Anders Wanhainen, Sverker Svensjö
Objective/BackgroundThe cost-effectiveness of screening depends on the cost of screening, prevalence of asymptomatic carotid artery stenosis (ACAS), and the potential effect of medical intervention in reducing the risk of stroke. The aim of the study was to determine the threshold values for these parameters in order for screening for ACAS to be cost-effective.MethodsThe clinical effect and cost-effectiveness of ultrasound screening for ACAS with subsequent initiation of preventive therapy versus not screening was assessed in a Markov model with a lifetime perspective. Key parameters, including stroke risk, all cause mortality, and costs, were based on contemporary published data, population statistics, and data from an ongoing screening program in Uppsala county (population 300,000), Sweden. Prevalence of ACAS (2%) and the rate of best medical treatment (BMT; 40%) were based on data from a male Swedish population recently screened for ACAS. The required stroke risk reduction from BMT, incremental cost-efficiency ratio (ICER), absolute risk reduction for stroke (ARR), and number needed to screen (NNS) were calculated.ResultsScreening was cost-effective at an ICER of €5744 per incremental quality adjusted life year (QALY) gained. ARR was 135 per 100,000 screened, NNS was 741, and QALYs gained were 6700 per 100,000 invited. At a willingness to pay (WTP) threshold of €50,000 per QALY the minimum required stroke risk reduction from BMT was 22%. The assumed degree of stroke risk reduction was the most important determinant of cost-efficiency.ConclusionA moderate (22%) reduction in the risk of stroke was required for an ACAS screening strategy to be cost-effective at a WTP of €50,000/QALY. Targeting populations with a higher prevalence of ACAS could further improve cost-efficiency.



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Combined Impact of Chronic Kidney Disease and Contrast Induced Acute Kidney Injury on Long-term Outcomes in Patients with Acute Lower Limb Ischaemia

Publication date: Available online 7 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Petar Zlatanovic, Igor Koncar, Marko Dragas, Nikola Ilic, Milos Sladojevic, Perica Mutavdzic, Ivan Tomic, Dusan Kostic, Lazar Davidovic
IntroductionAcute lower limb ischaemia (ALI) is the sudden onset of decreased arterial perfusion with imminent threat to limb viability. Contrast induced acute kidney injury (CI-AKI) is one of the complications that increases mortality in patients who undergo contrast imaging in coronary procedures. The goal of this study is to evaluate the impact of chronic kidney disease (CKD) and CI-AKI on long-term clinical outcomes in patients with ALI undergoing lower limb revascularisation.MethodsA total 1017 consecutive patients with acute lower limb ischaemia who were admitted between July 1, 2006, and January 1, 2017, were retrospectively reviewed. Patients who had end stage renal disease, those who had end stage heart and malignant disease and died within 7 days of limb revascularisation, and those who did not undergo angiography were excluded. Thus 546 patients were included in the final analysis. Patients were classified as with or without CKD and were then subdivided according to the presence or absence of the development of CI-AKI, defined as an increase in serum creatinine of ≥0.5 mg/dL or by ≥25% from the baseline value within the first 72 h after contrast exposure. The primary end point was all cause mortality and secondary major adverse limb event (MALE).ResultsBoth CKD and CI-AKI were associated with the highest rate of all cause mortality (chi square = 55.77, d.f. = 1, p < .01, log rank test) and MALE (chi square = 79.07, d.f. = 1, p < .01, log rank test). The presence of CKD and CI-AKI were significant risk factors associated with long-term all cause mortality (HR = 2.61, p < .01) and MALE (HR = 2.87, p < .01).ConclusionIn patients with ALI undergoing lower limb revascularisation, both CKD and CI-AKI were significantly associated with poor long-term outcomes compared with either CKD or CI-AKI alone. Further studies are required to assess this association and to confirm the combined effect of CKD and CI-AKI on long-term clinical outcomes.



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Elective Repair of Abdominal Aortic Aneurysm and the Risk of Colonic Ischaemia: Systematic Review and Meta-Analysis

Publication date: Available online 7 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jeremy S. Williamson, Graeme K. Ambler, Christopher P. Twine, Ian M. Williams, Gethin Ll. Williams
IntroductionColon ischaemia (CI) is a significant complication of open (OR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With a rapid increase in EVAR uptake, contemporary data demonstrating the differing rates and outcomes of CI between EVAR and OR, particularly in the elective setting, are lacking. The aim was to characterise the risk and consequences of CI in elective AAA repair comparing EVAR with OR.MethodsA systematic review and meta-analysis of the literature was performed using the Cochrane collaboration protocol and reported according to the PRISMA guidelines. PubMed, MedLine, and EMBASE were searched for studies reporting CI rates after elective AAA repair. Ruptured AAAs were excluded from analysis.ResultsThirteen studies reporting specific outcomes of CI after elective AAA repair, containing 162,750 evaluable patients (78,151 EVAR and 84,599 OR) were included. All studies found a higher risk of CI with OR than with EVAR. Three studies performed confounder adjustment with CI rates of 0.5–1% versus 2.1–3.6% (EVAR vs. OR) and combined odds ratio of 2.7 (2.0–3.5) for the development of CI with OR versus EVAR. The majority of cases of CI occurred within 30 days and were associated with variable mortality (0–73%) and re-intervention rates (27–54%). GRADE assessment of evidence strength was very low for all outcomes. There was a high degree of heterogeneity between studies both methodologically and in terms of CI rates, re-intervention, mortality, and time to development of CI.ConclusionsEVAR is associated with a reduced incidence of CI compared with OR.



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Additional physical therapy services reduce length of stay and improve health outcomes in people with acute and sub-acute conditions: an updated systematic review and meta-analysis

Publication date: Available online 7 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Casey L. Peiris, Nora Shields, Natasha K. Brusco, Jennifer J. Watts, Nicholas F. Taylor
ObjectiveTo update a previous review on whether additional physical therapy services reduce length of stay, improve health outcomes, are safe and cost effective for patients with acute or sub-acute conditions.Data sourcesElectronic database (AMED, CINAHL, EMBASE, MEDLINE, PEDro, PubMed) searches were updated from 2010 through June 2017.Study selectionRandomized controlled trials evaluating additional physical therapy services on patient health outcomes, length of stay or cost effectiveness were eligible. Searching identified 1524 potentially relevant articles, of which 11 new articles from 8 new randomized controlled trials with 1563 participants were selected. In total, 24 randomized controlled trials with 3262 participants are included in this review.Data extractionData were extracted using the form used in the original systematic review. Methodological quality was assessed using the PEDro scale and The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was applied to each meta-analysis.Data synthesisPost intervention data were pooled with an inverse variance, random effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs). There is moderate quality evidence that additional physical therapy services reduced length of stay by 3 days in sub-acute settings (MD-2.8, 95%CI -4.6 to -0.9, I² 0%) and low quality evidence that it reduced length of stay by 0.6 days in acute settings (MD -0.6, 95%CI -1.1 to 0.0, I² 65%). Additional physical therapy led to small improvements in self-care (SMD 0.11, 95%CI 0.03 to 0.19, I² 0%), activities of daily living (SMD 0.13, 95%CI 0.02 to 0.25, I² 15%) and health-related quality of life (SMD 0.12, 95%CI 0.03 to 0.21, I² 0%), with no increases in adverse events. There was no significant change in walking ability. One trial reported that additional physical therapy was likely to be cost-effective in sub-acute rehabilitation.ConclusionsAdditional physical therapy services improve patient activity and participation outcomes, while reducing hospital length of stay for adults. These benefits are likely safe and there is preliminary evidence to suggest they may be cost effective.



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Presurgical pazopanib for renal cell carcinoma with inferior vena caval thrombus: a single-institution study

The aim of this study was to investigate the clinical benefit of presurgical therapy with pazopanib in renal cell carcinoma (RCC) patients with a tumor thrombus extending to a high level in the vena cava. A retrospective review was performed for seven consecutive patients with RCC and tumor thrombus involving the vena cava above the hepatic vein (level 3–4, Mayo Clinic classification) treated with pazopanib without initial cytoreductive nephrectomy at our institution. The effect of pazopanib was assessed in terms of the primary site response, thrombus diameter, and height (before and after treatment) on computed tomography or MRI. The tumor thrombus level before the induction of pazopanib was 3 in one patient and 4 in the remaining six patients. After pazopanib, shrinkage of the primary site and thrombus diameter and length were observed in all patients except one (with a rhabdoid tumor). The mean decreases of primary tumor diameter, tumor thrombus diameter, and length were 14, 9, and 31 mm, respectively. The tumor thrombus level decreased in three (43%) patients and remained stable in the remaining patient. Our findings suggest that presurgical treatment with pazopanib may shrink the tumor thrombus and decrease the surgical invasiveness in RCC patients with a high-level tumor thrombus. Correspondence to Tomoaki Terakawa, PhD, MD, Department of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuoku, Kobe 650-0017, Hyogo Prefecture, Japan Tel: +81 78 382 6155; fax: +81 78 382 6169; e-mail: daatera0804@hotmail.com Received October 17, 2017 Accepted March 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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What you should not miss from the systematic reviews and meta-analyses on allergen-specific immunotherapy in 2017

Purpose of review Allergen immunotherapy (AIT) is a well recognized and extensively studied therapeutic intervention for some allergic diseases. Every year new systematic reviews and meta-analysis provide the most powerful source of evidence to orient decision making on prevention or efficacy of AIT. We here discuss systematic reviews and meta-analyses on AIT (published January 2017 to February 2018). Recent findings We identified 4 systematic reviews and 10 meta-analyses. Subcutaneous and sublingual AIT (SCIT/SLIT) significantly reduced the development of asthma in children–adolescents with moderate/severe allergic rhinitis, but evidence for a short-term, preventive effect for new allergic sensitizations was nonconclusive. SCIT/SLIT proved to significantly improve symptom and medication scores versus placebo or active comparators in respiratory allergy, with various effect sizes. Oral immunotherapy for IgE-mediated food allergy resulted in substantial benefit in desensitization rates. Data on venom AIT and latex AIT, although limited in quantity and quality, respectively, suggest a large and discrete beneficial effect. Summary Although current evidence extracted from meta-analyses and systematic reviews support AIT as an effective, relatively safe, and well tolerated alternative for some allergic diseases, heterogeneity and some methodological inconsistencies represent matters of concern as they may affect the validity and applicability of their results, especially in the context of individual, real-life settings. Correspondence to Désirée Larenas-Linnemann, MD, Hospital Medica Sur, Torre 2-602, Colonia Toriello-Guerra, Delegación Tlalpan, 14050 Mexico city, Mexico. Tel: +52 1 55 85095950; fax: +52 55 51712248; e-mail: marlar1@prodigy.net.mx Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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How to actively treat food allergy

Purpose of review In the last years, food allergy treatment is moving away from food avoidance to interventional treatments. We review here the recent developments on immunotherapy with food allergens. Recent findings Oral immunotherapy remains the best studied form of food immunotherapy. In 2017, further evidence has been added to its efficacy. Its mechanisms of action are under scrutiny. To reduce its side effects, studies have been dedicated to the simultaneous use of biologics, in particular omalizumab. Among the other forms of food immunotherapy that are being developed, the epicutaneous application of food allergens is promising. Summary The immunologic trajectories of the development of food tolerance may be intercepted by different forms of food immunotherapy. Research efforts aim to make these therapies feasible at the clinical level. Correspondence to Valentina Pecora, MD, PhD, Allergy Department, Pediatric Hospital Bambino Gesù – Piazza di Sant'Onofrio 4, Vatican City, Rome 00100, Italy. Tel: +39 46 6859 4777; fax: +39 46 6859 2020; e-mail: valentina.pecora@opbg.net Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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How to manage food dependent exercise induced anaphylaxis (FDEIA)

Purpose of review In recent years, the number of reports on food-dependent exercise-induced anaphylaxis (FDEIA) has been increasing. This review aims to describe the standard management of FDEIA including provocation tests and identify the issues that remain unclear. Recent findings Provocation tests with aspirin for FDEIA enable us to confirm the definitive diagnosis and to make differential diagnosis. In some cases, FDEIA symptoms can be induced by aspirin and the causative food without exercise. Exercise may only be an augmenting factor of FDEIA, similar to aspirin or alcohol. Summary The mechanisms of FDEIA development remain unclear. It has been suggested that in FDEIA, exercise lowers the threshold of a food allergy. Further research is needed to elucidate the mechanism of FDEIA and to establish strategies for effective disease management. Correspondence to Tomoyuki Asaumi, Department of Pediatrics, Sagamihara National Hospital, 18-1, Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan. Tel: +81 42 742 8311; fax: +81 42 742 5314; e-mail: ocean19oranges@yahoo.co.jp Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Differences between manual and automatic analysis in determining the severity of Obstructive Sleep Apnea using home sleep apnea testing

Publication date: Available online 7 April 2018
Source:Sleep Medicine
Author(s): Gonzalo Labarca, Jorge Dreyse, Constanza Salas, Andrea Contreras, Gonzalo Nazar, Maria I. Gaete, Jorge Jorquera
IntroductionHome sleep apnea testing (HSAT) is a diagnostic measure for obstructive sleep apnea hypopnea syndrome (OSAHS) in moderate/high risk patients. Some HSAT companies contain automatic analysis (AA). However, guidelines recommend manual analysis (MA) despite the weak evidence for this recommendation.ObjectiveEvaluate the concordance between AA and MA of HSAT to make either a diagnosis and severity classification.MethodsWe evaluated AA and MA of HSAT between 2015 to 2016. The study was a blind analysis reviewed by two physicians using currents recommendations. The differences between AA and MA were compared with single variable T analysis, inter-scorer agreement for diagnosis was evaluated with Cohen Kappa coefficient, correlation was examined using Tau-b Kendall, and Bland-Altman plot was constructed to analyze differences between AA and MA.Results198 patients were included. Mean age was 50 ±15 years, 83% male, BMI 30 ±5 and neck circumference 41 ±4 cm. Eighty-two percent of subjects showed an apnea-hypopnea index (AHI) > 5 ev/hr. Thirty-five percent of patients with OSAHS were mild (AHI: 5-15 ev/hr.), 34% moderate and 31% severe (>30 ev/hr.). The kappa coefficient between physicians was 1.0 (high), between AA and MA was 0.58 (moderate) for the diagnosis of OSAHS and 0.33 (weak) for severity with 0.70 Tau-b. The AA underestimates the IAH -8 ev/hr., (95% CI -9 to -7 ev/hr.,p<0.001) and delivers a misclassification of severity by 47%. Conclusions: AA underestimates the rate of respiratory events and alters the classification of the severity of the disease and may modify the therapeutic approach.



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Abnormal gray matter asymmetry in alcohol dependence

Previous voxel-based morphometry studies have provided evidence that patients with alcohol dependence (AD) have widespread gray matter morphological abnormalities. However, brain structural asymmetry in AD has not been assessed to date. Here, we aimed to use a recently developed voxel-based morphometry-based approach to investigate global and regional gray matter asymmetry alterations in AD. A total of 39 male individuals, including 19 AD patients and 20 age-matched healthy controls, underwent high-resolution structural MRI. Global and voxel-wise gray matter asymmetries were measured separately by the Dice coefficient and the asymmetry index, which were compared between the two groups. We found no difference in the global gray matter asymmetry between AD patients and healthy controls. However, voxel-wise gray matter asymmetry analysis showed that AD patients and healthy controls had different distribution patterns of brain regions with a rightward asymmetry and a leftward asymmetry Furthermore, we observed an increased rightward asymmetry of gray matter in the hemispheric I–IV and V of the cerebellum and lingual gyrus in AD patients. These findings suggest that abnormal structural asymmetry in the cerebellum and the primary visual cortex may be the neural mechanisms contributing toward motor and visual impairments in AD. Correspondence to Yongqiang Yu, PhD, Department of Radiology, the First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei 230022, Anhui Province, China Tel/fax: +86 0551 6292 3494; e-mail: cjr.yuyongqiang@vip.163.com Received March 5, 2018 Accepted March 19, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Hibernoma Mimicking Atypical Lipomatous Tumor: 64 Cases of a Morphologically Distinct Subset

Hibernoma is a benign adipocytic tumor with predilection for subcutaneous tissue of the thigh, upper trunk, and neck of middle-aged adults. 11q13 rearrangement resulting in MEN1/AIP codeletion is characteristic. Hibernomas are composed, in varying proportions, of brown fat cells, mature adipocytes, and microvacuolated lipoblast-like cells. Examples containing predominantly multivacuolated lipoblast-like cells are uncommon and distinction from atypical lipomatous tumor (ALT) is important for clinical management. We herein present the clinicopathologic features of 64 hibernomas histologically mimicking ALT. MDM2 and CDK4 immunohistochemistry as well as MDM2 fluorescence in situ hybridization were performed in a subset of cases. Clinical and follow-up information were obtained from referring pathologists. Thirty-four patients were male and 30 female, with a median age of 43 years (range, 24 to 78 y). The tumors were well circumscribed and mostly deeply located (53/64 cases, 83%) with a median tumor size of 12.9 cm (range, 3.5 to 23 cm) and predilection for the thigh (42/64 cases, 66%). Histologically, large cells with prominent lipoblast-like cytoplasmic fatty vacuoles and small central nuclei were present to a prominent degree in all cases, along with mature univacuolated adipocytes and smaller numbers of large, finely vacuolated cells with eosinophilic granular cytoplasm. Nuclear atypia and mitoses were absent. None of the 39 cases tested showed CDK4 and MDM2 overexpression or MDM2 amplification. Follow-up, available for 16/64 cases (median, 47 mo; range, 1 to 165 mo), revealed no recurrences or metastases. Hibernoma mimicking ALT shows predilection for deep soft tissue, especially in the thigh. These tumors behave in a benign manner and MDM2/CDK4 negativity may be useful in excluding ALT. Present address: Youssef Al Hmada, MD, Department of Pathology, University of Mississippi, Graduate School of Medicine, Jackson, MS. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Christopher D.M. Fletcher, MD, FRCPath, Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115 (e-mail: cfletcher@bwh.harvard.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Self-reported anxiety and depression unchanged after endoscopic sinus surgery for chronic rhinosinusitis.

Self-reported anxiety and depression unchanged after endoscopic sinus surgery for chronic rhinosinusitis.

Rhinology. 2018 Apr 08;:

Authors: Adams KN, Schuman TS, Ebert CS, You W, Tomoum MO, Senior BA

Abstract
BACKGROUND: Prior research has established that anxiety and depression, as measured by the Hospital Anxiety Depression Score (HADS), are strongly correlated with disease-specific quality of life (Rhinosinusitis Disability Index - RSDI) in chronic rhinosinusitis (CRS). We hypothesized that anxiety and depression would decrease after functional endoscopic sinus surgery (FESS), and furthermore that HADS would predict improvement in RSDI following surgery.
METHODOLOGY: The study cohort from 2014 consisted of 99 CRS patients who underwent nasal endoscopy, RSDI, and HADS evaluation. The cohort was segregated by whether or not they underwent FESS and an updated HADS was administered. For 44 surgical patients, pre- and post-operative RSDI (n=38), Lund-Kennedy (LK) (n=34) and HADS (n=18) scores were compared. Delta RSDI was compared between patients with varying levels of anxiety and depression.
RESULTS: Lund-Kennedy scores improved from 5.8 ± 4.1 to 3.2 ± 2.6 following surgery, as did total RSDI (39.3 ± 26.8 to 24.6 ± 29.2). Total HADS (9.8 ± 6.4 to 11.3 ± 7.4) and depression and anxiety subscores were unchanged. Linear regression did not reveal a correlation between HADS and change in RSDI following FESS. Delta RSDI was not significantly different between patients with varying levels of anxiety and depression.
CONCLUSIONS: Despite improvements in objective evidence of sinonasal inflammation (LK) and disease-specific quality of life (RSDI), neither depression nor anxiety improved after FESS, nor did the magnitude of psychological comorbidity predict post-operative improvement in quality of life. Improvement in RSDI was not different among patients with varying levels of anxiety and depression. Levels of depression and anxiety may be hard-wired, and therefore not influenced by changes in objective or perceived sinonasal disease burden.

PMID: 29626844 [PubMed - as supplied by publisher]

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Effect of voice therapy on vocal fold polyp treatment.

Related Articles

Effect of voice therapy on vocal fold polyp treatment.

Eur Arch Otorhinolaryngol. 2018 Apr 06;:

Authors: Sahin M, Gode S, Dogan M, Kirazli T, Ogut F

Abstract
PURPOSE: To investigate the role of voice therapy (VT) and factors that may affect the response to VT in the treatment of vocal fold polyps, especially as a complement to phonosurgery.
METHODS: Retrospective review of patients with vocal fold polyp undergoing surgery and/or VT in a tertiary medical center. The demographic data, phoniatric history, videolaryngostroboscopic findings, polyp characteristics, VHI-10 and GRB scores, and voice analysis data were recorded before and after the treatment. The patients were grouped as those who had undergone endolaryngeal microsurgery only (Group S), those who had first received VT then undergone surgery due to inadequate VT outcome (Group VTpS), and those who had only undergone VT with a follow-up plan (Group VT).
RESULTS: Data were reviewed from 211 (108 M, 103 F) patients with a mean age of 41.3 ± 11 years. The improvement in all voice-related variables observed in the S and VTpS groups was significantly greater compared to the VT group despite the degree of improvement achieved in this group. At the end of the treatment period, improvements in G-R-B, VHI-10 and stroboscopy scores were significantly greater in the VTpS group than in the S and VT groups.
CONCLUSION: Voice therapy can improve voice quality to some extent during the treatment of vocal fold polyps. However, VT alone is unsatisfactory compared to surgery alone. Pre-surgical VT can enhance the ultimate success of treatment. A young age, small polyps, and short duration of dysphonia may increase the possibility of benefiting from VT.

PMID: 29626250 [PubMed - as supplied by publisher]

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A Randomized Comparison Between Interscalene and Small-Volume Supraclavicular Blocks for Arthroscopic Shoulder Surgery

Background and Objectives This randomized trial compared ultrasound (US)–guided interscalene block (ISB) and small-volume supraclavicular block (SCB) for arthroscopic shoulder surgery. We hypothesized that SCB would provide equivalent analgesia to ISB 30 minutes after surgery without the risk of hemidiaphragmatic paralysis (HDP). Methods All patients received an US-guided intermediate cervical plexus block. In the ISB group, US-guided ISB was performed with 20 mL of levobupivacaine 0.5% and epinephrine 5 μg/mL. In the SCB group, US-guided SCB was carried out using 20 mL of the same local anesthetic agent: 3 and 17 mL were deposited at the "corner pocket" (ie, intersection of the first rib and subclavian artery) and posterolateral to the brachial plexus, respectively. A blinded investigator assessed ISBs and SCBs every 5 minutes until 30 minutes using a composite scale that encompassed the sensory function of the supraclavicular nerves, the sensorimotor function of the axillary nerve, and the motor function of the suprascapular nerve. We considered the blocks complete if, at 30 minutes, a composite score equal or superior to 6 points (out of 8 points) was achieved. Thus, onset time was defined as the time required to reach a minimal composite score of 6 points. The blinded investigator also assessed the presence of HDP at 30 minutes with US. Subsequently, all patients underwent general anesthesia. Postoperatively, a blinded investigator recorded pain scores at rest at 0.5, 1, 2, 3, 6, 12, and 24 hours. Patient satisfaction at 24 hours, consumption of intraoperative and postoperative narcotics, and opioid-related adverse effects were also tabulated. Results Both groups displayed equivalent postoperative pain scores at 0.5, 1, 2, 3, 6, 12, and 24 hours. Interscalene blocks resulted in a higher incidence of HDP (95% vs 9%; P

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Effective Dose of Intravenous Dexmedetomidine to Prolong the Analgesic Duration of Interscalene Brachial Plexus Block: A Single-Center, Prospective, Double-Blind, Randomized Controlled Trial

Background and Objectives Intravenous (IV) dexmedetomidine (DEX) is reported to prolong the analgesic duration after single-shot interscalene brachial plexus block (ISBPB). However, the effective analgesic dose of IV DEX remains undetermined. Therefore, we aimed to elucidate the clinically relevant dose of IV DEX to prolong the analgesic duration of ISBPB. Methods Seventy-two patients scheduled for arthroscopic shoulder surgery received ISBPB with 15 mL of 0.5% ropivacaine with 1:200,000 epinephrine and were randomly assigned to 1 of 4 groups (n = 18, each): (1) IV normal saline (control), (2) IV DEX 0.5 μg/kg (DEX 0.5), (3) IV DEX 1.0 μg/kg (DEX 1.0), and (4) IV DEX 2.0 μg/kg (DEX 2.0). The primary outcome was time to the first pain at surgical site. Results The median (interquartile range) duration of analgesia was significantly prolonged for the DEX 2.0 (874 minutes [727–1153 minutes]) compared with 656 minutes (590–751 minutes), 703 minutes (644–761 minutes), and 696 minutes (615–814 minutes) for the control, DEX 0.5 and DEX 1.0 groups, respectively (P = 0.001, P = 0.008, and P = 0.003, respectively). Postoperative cumulative IV morphine equivalent consumption at 24 hours was significantly lower in the DEX 2.0 compared with the control, DEX 0.5 and DEX 1.0 groups (P

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Perineural Versus Systemic Dexamethasone in Front-Foot Surgery Under Ankle Block: A Randomized Double-Blind Study

Background and Objectives Among the different adjuvants, dexamethasone is one of the most accepted to prolong the effect of local anesthetics. This study aims to determine the superiority of perineural over systemic dexamethasone administration after a single-shot ankle block in metatarsal osteotomy. Methods We performed a prospective, double-blind, randomized study. A total of 100 patients presenting for metatarsal osteotomy with an ankle block were randomized into 2 groups: 30 mL ropivacaine 0.375% + perineural dexamethasone 4 mg (1 mL) + 2.5 mL of systemic saline solution (PNDex group, n = 50) and 30 mL ropivacaine 0.375% + 1 mL of perineural saline solution + intravenous dexamethasone 10 mg (2.5 mL) (IVDex group, n = 50). The primary end point was the duration of analgesia defined as the time between the performance of the ankle block and the first administration of rescue analgesia with tramadol. Results Time period to first rescue analgesia with tramadol was similar in the IVDex group and the PNDex group. Data are expressed as mean (SD) or median (range). Duration of analgesia was 23.2 (9.5) hours in the IVDex group and 19 (8.2) hours in the PNDex group (P = 0.4). Consumption of tramadol during the first 48 hours was 0 mg (0–150 mg) in the IVDex group versus 0 mg (0–250 mg) in the PNDex group (P = 0.59). Four (8%) and 12 (24%) patients reported nausea or vomiting in the IVDex group and the PNDex group, respectively (P = 0.03). Conclusions In front-foot surgery, perineural and systemic administrations of dexamethasone are equivalent for postoperative pain relief when used as an adjuvant to ropivacaine ankle block. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02904538. Address correspondence to: Philippe Marty, MD, Department of Anesthesia, Clinique Médipôle Garonne, 31036, Toulouse, France (e-mail: philippemarty@hotmail.com). Accepted for publication November 20, 2017. The authors declare no conflict of interest. Support was provided solely from institutional and department sources from Department of Anesthesiology, Clinique Médipôle Garonne, Toulouse, France. This work should be attributed to the Department of Anesthesiology, Clinique Médipôle Garonne, Toulouse, France. Authors' contributions: O.R., B.Basset, C.V., and M.C.M. performed all regional anesthesia. P.M. and F.F. wrote the manuscript. C.M., M.M., and M.C. participated in the design of the study. B.Bataille performed the statistical analysis. A.D. participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Practice Management: Successfully Guiding Your Group into the Future

Publication date: Available online 7 April 2018
Source:Anesthesiology Clinics
Author(s): Lee A. Fleisher




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Effect of voice therapy on vocal fold polyp treatment.

Related Articles

Effect of voice therapy on vocal fold polyp treatment.

Eur Arch Otorhinolaryngol. 2018 Apr 06;:

Authors: Sahin M, Gode S, Dogan M, Kirazli T, Ogut F

Abstract
PURPOSE: To investigate the role of voice therapy (VT) and factors that may affect the response to VT in the treatment of vocal fold polyps, especially as a complement to phonosurgery.
METHODS: Retrospective review of patients with vocal fold polyp undergoing surgery and/or VT in a tertiary medical center. The demographic data, phoniatric history, videolaryngostroboscopic findings, polyp characteristics, VHI-10 and GRB scores, and voice analysis data were recorded before and after the treatment. The patients were grouped as those who had undergone endolaryngeal microsurgery only (Group S), those who had first received VT then undergone surgery due to inadequate VT outcome (Group VTpS), and those who had only undergone VT with a follow-up plan (Group VT).
RESULTS: Data were reviewed from 211 (108 M, 103 F) patients with a mean age of 41.3 ± 11 years. The improvement in all voice-related variables observed in the S and VTpS groups was significantly greater compared to the VT group despite the degree of improvement achieved in this group. At the end of the treatment period, improvements in G-R-B, VHI-10 and stroboscopy scores were significantly greater in the VTpS group than in the S and VT groups.
CONCLUSION: Voice therapy can improve voice quality to some extent during the treatment of vocal fold polyps. However, VT alone is unsatisfactory compared to surgery alone. Pre-surgical VT can enhance the ultimate success of treatment. A young age, small polyps, and short duration of dysphonia may increase the possibility of benefiting from VT.

PMID: 29626250 [PubMed - as supplied by publisher]

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Effect of voice therapy on vocal fold polyp treatment.

Related Articles

Effect of voice therapy on vocal fold polyp treatment.

Eur Arch Otorhinolaryngol. 2018 Apr 06;:

Authors: Sahin M, Gode S, Dogan M, Kirazli T, Ogut F

Abstract
PURPOSE: To investigate the role of voice therapy (VT) and factors that may affect the response to VT in the treatment of vocal fold polyps, especially as a complement to phonosurgery.
METHODS: Retrospective review of patients with vocal fold polyp undergoing surgery and/or VT in a tertiary medical center. The demographic data, phoniatric history, videolaryngostroboscopic findings, polyp characteristics, VHI-10 and GRB scores, and voice analysis data were recorded before and after the treatment. The patients were grouped as those who had undergone endolaryngeal microsurgery only (Group S), those who had first received VT then undergone surgery due to inadequate VT outcome (Group VTpS), and those who had only undergone VT with a follow-up plan (Group VT).
RESULTS: Data were reviewed from 211 (108 M, 103 F) patients with a mean age of 41.3 ± 11 years. The improvement in all voice-related variables observed in the S and VTpS groups was significantly greater compared to the VT group despite the degree of improvement achieved in this group. At the end of the treatment period, improvements in G-R-B, VHI-10 and stroboscopy scores were significantly greater in the VTpS group than in the S and VT groups.
CONCLUSION: Voice therapy can improve voice quality to some extent during the treatment of vocal fold polyps. However, VT alone is unsatisfactory compared to surgery alone. Pre-surgical VT can enhance the ultimate success of treatment. A young age, small polyps, and short duration of dysphonia may increase the possibility of benefiting from VT.

PMID: 29626250 [PubMed - as supplied by publisher]

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Molecular markers in well-differentiated thyroid cancer.

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Molecular markers in well-differentiated thyroid cancer.

Eur Arch Otorhinolaryngol. 2018 Apr 06;:

Authors: D'Cruz AK, Vaish R, Vaidya A, Nixon IJ, Williams MD, Vander Poorten V, López F, Angelos P, Shaha AR, Khafif A, Skalova A, Rinaldo A, Hunt JL, Ferlito A

Abstract
PURPOSE: Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described.
METHODS: PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review.
RESULTS: There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult.
CONCLUSION: The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

PMID: 29626249 [PubMed - as supplied by publisher]

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Evaluating off-label uses of acetazolamide.

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Evaluating off-label uses of acetazolamide.

Am J Health Syst Pharm. 2018 Apr 15;75(8):524-531

Authors: Van Berkel MA, Elefritz JL

Abstract
PURPOSE: Current off-label uses of acetazolamide in hospitalized patients are reviewed.
SUMMARY: Acetazolamide is a carbonic anhydrase inhibitor typically used for indications including epilepsy, glaucoma, edema, and altitude sickness but it may be prescribed in hospitalized patients for off-label indications. It inhibits carbonic anhydrase, which leads to reduced hydrogen ion secretion in the proximal renal tubule, resulting in increased bicarbonate and cation excretion and causing urinary alkalization and diuresis. In addition, acetazolamide decreases the production of cerebrospinal fluid (CSF) and aqueous humor, reducing intracranial pressure (ICP) and intraocular pressure. This allows acetazolamide to be used for treatment of idiopathic intracranial hypertension and elevated ICP due to CSF leaks to avoid invasive procedures. It is a sulfonamide derivative, with dosages ranging from 250 to 4,000 mg daily divided every 6-12 hours. The plasma half-life is 4-8 hours, though the pharmacologic effects of acetazolamide last longer. Acetazolamide is highly protein bound and primarily eliminated by the kidneys, so administration should not be more frequent than every 12 hours if creatinine clearance is less than 50 mL/min. Limited literature exists describing the optimal patients to receive acetazolamide therapy.
CONCLUSION: The potential benefits of acetazolamide include ventilator weaning for chronic obstructive pulmonary disease patients, avoidance of invasive procedures in patients with a CSF leak or elevated ICP, and prevention of high-dose methotrexate toxicity and contrast-induced nephropathy. Uncertainty remains regarding the selection of patients who would best benefit from acetazolamide use.

PMID: 29626002 [PubMed - in process]

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The important role of the peer reviewer.

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The important role of the peer reviewer.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2018 Mar 19;:

Authors: Lubek JE

PMID: 29625830 [PubMed - as supplied by publisher]

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A Computerized Tomography Study of Vocal Tract Setting in Hyperfunctional Dysphonia and in Belting.

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A Computerized Tomography Study of Vocal Tract Setting in Hyperfunctional Dysphonia and in Belting.

J Voice. 2018 Apr 03;:

Authors: Saldias M, Guzman M, Miranda G, Laukkanen AM

Abstract
BACKGROUND: Vocal tract setting in hyperfunctional patients is characterized by a high larynx and narrowing of the epilaryngeal and pharyngeal region. Similar observations have been made for various singing styles, eg, belting. The voice quality in belting has been described to be loud, speech like, and high pitched. It is also often described as sounding "pressed" or "tense". The above mentioned has led to the hypothesis that belting may be strenuous to the vocal folds. However, singers and teachers of belting do not regard belting as particularly strenuous.
PURPOSE: This study investigates possible similarities and differences between hyperfunctional voice production and belting. This study concerns vocal tract setting.
METHODS: Four male patients with hyperfunctional dysphonia and one male contemporary commercial music singer were registered with computerized tomography while phonating on [a:] in their habitual speaking pitch. Additionally, the singer used the pitch G4 in belting. The scannings were studied in sagittal and transversal dimensions by measuring lengths, widths, and areas.
RESULTS: Various similarities were found between belting and hyperfunction: high vertical larynx position, small hypopharyngeal width, and epilaryngeal outlet. On the other hand, belting differed from dysphonia (in addition to higher pitch) by a wider lip and jaw opening, and larger volumes of the oral cavity.
CONCLUSIONS: Belting takes advantage of "megaphone shape" of the vocal tract. Future studies should focus on modeling and simulation to address sound energy transfer. Also, they should consider aerodynamic variables and vocal fold vibration to evaluate the "price of decibels" in these phonation types.

PMID: 29625720 [PubMed - as supplied by publisher]

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The relationship between mismatch response and the acoustic change complex in normal hearing infants

Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Kristin M. Uhler, Sharon K. Hunter, Elyse Tierney, Phillip M. Gilley
ObjectiveTo examine the utility of the mismatch response (MMR) and acoustic change complex (ACC) for assessing speech discrimination in infants.MethodsContinuous EEG was recorded during sleep from 48 (24 male, 20 female) normally hearing aged 1.77 to –4.57 months in response to two auditory discrimination tasks. ACC was recorded in response to a three-vowel sequence (/i/-/a/-/i/). MMR was recorded in response to a standard vowel, /a/, (probability 85%), and to a deviant vowel, /i/, (probability of 15%). A priori comparisons included: age, sex, and sleep state. These were conducted separately for each of the three bandpass filter settings were compared (1–18, 1–30, and 1–40 Hz).ResultsA priori tests revealed no differences in MMR or ACC for age, sex, or sleep state for any of the three filter settings. ACC and MMR responses were prominently observed in all 44 sleeping infants (data from four infants were excluded). Significant differences observed for ACC were to the onset and offset of stimuli. However, neither group nor individual differences were observed to changes in speech stimuli in the ACC. MMR revealed two prominent peaks occurring at the stimulus onset and at the stimulus offset. Permutation t-tests revealed significant differences between the standard and deviant stimuli for both the onset and offset MMR peaks (p < 0.01). The 1–18 Hz filter setting revealed significant differences for all participants in the MMR paradigm.ConclusionBoth ACC and MMR responses were observed to auditory stimulation suggesting that infants perceive and process speech information even during sleep. Significant differences between the standard and deviant responses were observed in the MMR, but not ACC paradigm. These findings suggest that the MMR is sensitive to detecting auditory/speech discrimination processing.SignificanceThis paper identified that MMR can be used to identify discrimination in normal hearing infants. This suggests that MMR has potential for use in infants with hearing loss to validate hearing aid fittings.



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Eyeball pressure stimulation induces subtle sympathetic activation in patients with a history of moderate or severe traumatic brain injury

Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Ruihao Wang, Katharina M. Hösl, Fabian Ammon, Jörg Markus, Julia Koehn, Sankanika Roy, Mao Liu, Carmen de Rojas Leal, Dafin Muresanu, Steven R. Flanagan, Max J. Hilz
ObjectiveAfter traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation.MethodsIn 51 post-moderate-severe-TBI patients (32.7 ± 10.5 years old, 43.1 ± 33.4 months post-injury), and 30 controls (29.1 ± 9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04–0.15 Hz) and parasympathetic high (HF: 0.15–0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05).ResultsAt rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter.ConclusionsIn post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation.SignificanceOur findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI.



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Immunotherapy phase I trials in patients Older than 70 years with advanced solid tumours

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): H. Herin, S. Aspeslagh, E. Castanon, V. Dyevre, A. Marabelle, A. Varga, S. Postel Vinay, J.M. Michot, V. Ribrag, A. Gazzah, R. Bahleda, O. Mir, C. Massard, A. Hollebecque, J.C. Soria, C. Baldini
BackgroundThe development of immune checkpoint blocker development brings new hope in older patients (OPs) because of clinical efficacy and low toxicity. Clinical indications are rising steadily, but very few data are available in the geriatric population where comorbidities, reduced functional reserve and immunosenescence may affect efficacy and tolerance.MethodsAll cases of patients enrolled in immunotherapy phase I trials between January 2012 and December 2016 in the Drug Development Department (DITEP) at Gustave Roussy were retrospectively reviewed. Case–control analysis was performed in OPs (patients ≥ 70 years) matched to younger patients (YPs) (patients < 70 years) by trial and treatment dose. We compared cumulative incidence, grade and type of immune-related adverse events (IrAEs) and survival outcomes.ResultsAmong the 46 OPs and the 174 YPs enrolled in 14 phase I/II trials, 10 (22%) and 23 (13%) patients experienced grade III–IV IrAEs. Cumulative incidence of grade I–II IrAEs was significantly higher in OPs than YPs (p < 0.05). No significant difference was observed between the two groups for grade III–IV IrAEs (p = 0.50). Older age was not associated with lower dose intensity of treatment (p = 0.14). No significant difference was observed between OPs and YPs in median progression-free survival (hazards ratio 1.41, 95% confidence interval [CI] [0.94–2.11] p = 0.09) or median overall survival (HR 0.92, 95% CI [0.61–1.39] p = 0.77).ConclusionImmune checkpoint blockade appears to be an acceptable treatment option for OPs in the setting of phase I trials.



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Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Claire Bonneau, Gilles Paintaud, Olivier Trédan, Coraline Dubot, Céline Desvignes, Véronique Dieras, Sophie Taillibert, Patricia Tresca, Isabelle Turbiez, Jacques Li, Christophe Passot, Fawzia Mefti, Emmanuelle Mouret-Fourme, Emilie Le Rhun, Maya Gutierrez
PurposeLeptomeningeal carcinomatosis (MC) is commonly associated with HER2-positive breast cancer (HER2-BC), with a poor prognosis and no standardised treatment. We conducted a phase I dose-escalation study of intrathecal (IT) administration of trastuzumab in HER2-BC patients with MC to determine the maximum tolerated dose (MTD), which was based on both the achievement of a trastuzumab intra-cerebrospinal fluid concentration close to a conventional therapeutic plasma concentration (30 mg/L) and/or dose-limiting toxicity (DLT).MethodsThe protocol planned IT administration of trastuzumab (30 mg, 60 mg, 100 mg or 150 mg dose levels) once a week, over the course of at least 4 weeks. Sixteen patients with MC from HER2-BC received IT trastuzumab. Intra-cerebrospinal fluid samples were obtained before each injection for pharmacokinetics.ResultsWe did not observe DLT of IT trastuzumab. Eleven patients had no toxicity attributed to IT trastuzumab. For 60 mg or higher dose levels, minor toxicities attributed to IT trastuzumab included headache (2 patients), nausea (2 patients), vomiting (1 patient), cervical pain (1 patient) and peripheral neuropathy (1 patient). Two patients experienced immediate toxicity including headache or vomiting. The mean residual intra-cerebrospinal fluid concentration of trastuzumab was 27.9 mg/L for the 150 mg dose level. Three patients achieved a clinical response, seven patients had stable disease and four patients had progressive disease.ConclusionsThe MTD and recommended phase II weekly dose of IT trastuzumab in patients with HER2-BC and MC is 150 mg. A phase II trial using this dose regimen in MC from HER2-BC is ongoing.Registration identificationClinicalTrials.gov Identifier: NCT01373710 (https://ift.tt/2IAB1Op).



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Treatment decisions and the impact of adverse events before and during extended endocrine therapy in postmenopausal early breast cancer

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Erik J. Blok, Judith R. Kroep, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Hein Putter, Gerrit-Jan Liefers, Johan W.R. Nortier, Emiel J.Th. Rutgers, Caroline M. Seynaeve, Cornelis J.H. van de Velde
BackgroundExtended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome.MethodsIn the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS).ResultsNodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76–1.37).ConclusionsIn this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS.



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Bladder cancer survival: Women better off in the long run

Publication date: May 2018
Source:European Journal of Cancer, Volume 95
Author(s): Bettina Kulle Andreassen, Tom Kristian Grimsrud, Erik Skaaheim Haug
AimMortality among patients with bladder cancer is usually reported to be higher for women than men, but how the risk differs and why remain largely unexplained. We also described gender-specific differences in survival for patients with bladder cancer and estimated to what extent they can be explained by differences in T-stage distribution at the first diagnosis.MethodsThe present study comprised all 15,129 new cases of histologically verified invasive and non-invasive urothelial carcinoma of the urinary bladder diagnosed between 1997 and 2011 as registered in the Cancer Registry of Norway. Gender-specific excess mortality risk rates and risk ratios were calculated based on a flexible parametric relative survival model adjusting for T-stage and age, allowing the effect of gender to vary over time. We also present gender-specific relative survival curves for different T-stage patterns adjusted for age.ResultsRisk rates were significantly higher for women than men up to 2 years after bladder cancer diagnosis, particularly for muscle-invasive cancers. Thereafter, risk rates appeared to be higher in men. Adverse T-Stage distribution in women explained half of the unfavourable survival difference in female patients 2 years after diagnosis.ConclusionThe common view of worse bladder cancer prognosis in women than in men needs to be revised. Norwegian women have a less favourable prognosis solely within the first 2 years after diagnosis, particularly when diagnosed with a muscle-invasive tumour; parts of this discrepancy can be attributed to more severe initial diagnoses in women.



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Efficacy of cabazitaxel rechallenge in heavily treated patients with metastatic castration-resistant prostate cancer

Publication date: Available online 7 April 2018
Source:European Journal of Cancer
Author(s): Constance Thibault, Jean-Christophe Eymard, Alison Birtle, Michael Krainer, Giulia Baciarello, Aude Fléchon, Sylvestre Le Moulec, Dominique Spaeth, Brigitte Laguerre, Orazio Caffo, Jean-Laurent Deville, Phillipe Beuzeboc, Ali Hasbini, Marine Gross-Goupil, Carole Helissey, Mostefa Bennamoun, Anne-Claire Hardy-Bessard, Stéphane Oudard
BackgroundTreatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC.Patients and methodsClinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method. Data on toxicities were collected.ResultsA total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0–1 69%) were rechallenged with CABA (25 mg/m² q3w, 58%; 20 mg/m² q3w, 27.5%; other, 14.5%) for 1–10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3–15.7) from the first CABA rechallenge cycle, 59.9 months (47.8–67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4–90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders.ConclusionsCABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections.



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