Comprehensive evaluation of cytomorphologic, histologic, and molecular features of DICER1-altered thyroid lesions on FNA: A multipractice experience.

BACKGROUND: DICER1 mutations, though infrequent, are encountered on preoperative molecular testing of indeterminate adult and pediatric thyroid fine-needle aspiration (FNA) specimens. Yet, published cytomorphologic features of DICER1-altered thyroid lesions are limited. Cytomorphological features of DICER1-altered thyroid lesions were examined in a multipractice FNA cohort with clinical, radiological, and histologic data. METHODS: The cohort comprised 18 DICER1-altered thyroid FNAs, with 14 having slides available and eight having corresponding surgical resections. Smears, ThinPrep, and formalin-fixed cell block slides were reviewed and correlated with histology, when available. Clinical and radiologic data were obtained from the medical record. RESULTS: Most DICER1-altered FNAs were classified as atypia of undetermined significance (94.4%). DICER1 mutations occurred in codons 1709 (50%), 1810 (27.8%), and 1813 (22.2%). One patient had an additional DICER1 p.D1822N variant in both of their FNAs. Lesions were often hypoechoic (35.3%) and solid (47.1%) on ultrasound. Notable cytomorphologic features include mixed but prominent microfollicular or crowded component, variable colloid, and insignificant nuclear atypia. On resection (n = 10), histologic diagnoses ranged from benign follicular adenoma and low-risk follicular thyroid carcinoma to high-grade follicular-derived nonanaplastic thyroid carcinoma. Subcapsular infarct-type change was the most common histologic change. There was no evidence of recurrence or metastasis in eight patients on limited follow-up. CONCLUSION: DICER1-altered thyroid lesions occurred frequently in young females and FNAs show RAS-like cytomorphology including crowded, mixed macro-/microfollicular pattern, and bland nuclear features. On resection, DICER1-altered thyroid lesions include benign (50%), low-risk lesions (30%), or high-risk malignancies (20%).

Cytologic features of hepatic YAP1-TFE3 rearranged epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignancy, often with indolent behavior. Though most cases have a characteristic WWTR1-CAMTA1 gene fusion, a subtype of EHE with YAP1-TFE3 fusions and a distinct morphology has recently been described histologically, but no cases of YAP1-TFE3 EHE have been described in the cytology literature. We herein report on a case of YAP1-TFE3 fusion associated EHE diagnosed on fine-needle aspiration and core biopsy of a liver mass in an 18-year-old male patient who presented with synchronous lung and liver involvement. We also discuss the differential diagnosis of EHE on cytology specimens.

Characterising the vertical separation of shale-gas source rocks and aquifers across England and Wales (UK).

Shale gas is considered by many to have the potential to provide the UK with greater energy security, economic growth and jobs. However, development of a shale gas industry is highly contentious due to environmental concerns including the risk of groundwater pollution. Evidence suggests that the vertical separation between exploited shale units and aquifers is an important factor in the risk to groundwater from shale gas exploitation. A methodology is presented to assess the vertical separation between different pairs of aquifers and shales that are present across England and Wales. The application of the method is then demonstrated for two of these pairs-the Cretaceous Chalk Group aquifer and the Upper Jurassic Kimmeridge Clay Formation, and the Triassic sandstone aquifer and the Carboniferous Bowland Shale Formation. Challenges in defining what might be considered criteria for 'safe separation' between a shale gas formation and an overlying aquifer are discussed, in particular with respect to uncertainties in geological properties, aquifer extents and determination of socially acceptable risk levels. Modelled vertical separations suggest that the risk of aquifer contamination from shale exploration will vary greatly between shale-aquifer pairs and between regions and this will need to be considered carefully as part of the risk assessment and management for any shale gas development.

Le gaz de schiste est considéré par beaucoup comme ayant le potentiel de procurer au Royaume Uni une plus grande sécurité énergétique, une croissance économique et des emplois. Cependant, le développement de l'industrie du gaz de schiste est fortement contesté en raison des problèmes environnementaux, qui comprennent le risque de pollution des eaux souterraines. Des données probantes suggèrent que l'isolation verticale entre les unités de schistes exploitées et les aquifères est un facteur important vis-à-vis du risque de contamination des eaux souterraines associé à l'exploitation du gaz de schiste. Une méthodologie est proposée pour évaluer la séparation verticale entre différents couples aquifères­schistes présents en Angleterre et Pays de Galle. L'application de la méthode est ensuite décrite pour deux de ces couples, d'une part l'aquifère du Groupe de la Craie du Crétacé et la formation des Argiles du Kimméridgien (Jurassique supérieur), et l'aquifère des Grés du Trias et la formation carbonifère des schistes du Bowland. Les enjeux de la définition de ce qui pourrait être considéré comme critère d'une « isolation sécuritaire ¼ entre une formation à gaz de schiste et l'aquifère sus-jacent sont discutées, en particulier au regard des incertitudes sur les propriétés géologiques, l'extension des aquifères et la définition des niveaux de risques socialement acceptables. Les isolations verticales modélisées suggèrent que le risque de contamination d'un aquifère lié à une exploration du schiste variera grandement d'un couple schiste­aquifère à l'autre et d'une région à l'autre et que cela devra être examiné avec soin dans le cadre de l'évaluation du risque et de la gestion de tout développement du gaz de schiste.

Muchos consideran que el shale gas tiene el potencial de proporcionar al Reino Unido una mayor seguridad energética, crecimiento económico y empleos. Sin embargo, el desarrollo de una industria del shale gas es muy polémico debido a las preocupaciones ambientales, incluido el riesgo de contaminación del agua subterránea. La evidencia sugiere que la separación vertical entre las unidades de shale explotadas y los acuíferos es un factor importante en el riesgo para las aguas subterráneas en la explotación del shale. Se presenta una metodología para evaluar la separación vertical entre los diferentes pares de acuíferos y los shales que están presentes en Inglaterra y Gales. La aplicación del método se demuestra para dos de estos pares­el acuífero Chalk Group del Cretácico y la Kimmeridge Clay Formation del Jurásico Superior, y el acuífero de arenisca del Triásico y la Bowland Shale Formation del Carbonífero. Se discuten los desafíos para definir los que podrían considerarse criterios para una "separación segura" entre una formación de shale gas y un acuífero superpuesto, en particular con respecto a incertidumbres en las propiedades geológicas, extensiones de acuíferos y la determinación de niveles de riesgo socialmente aceptables. Las separaciones verticales modeladas sugieren que el riesgo de contaminación del acuífero por la exploración del shale variará mucho entre los pares de shale­acuífero y entre regiones, y esto deberá considerarse cuidadosamente como parte de la evaluación y gestión de riesgos para cualquier desarrollo de shale gas.

O gás de xisto é considerado um potencial fornecedor de maior segurança energética, crescimento econômico e empregos ao Reino Unido. Porém, o desenvolvimento de uma indústria de gás de xisto é altamente controverso devido a preocupações ambientais, como o risco de poluição das águas subterrâneas. Evidências sugerem que a separação vertical entre unidades de xisto exploradas e aquíferos é um fator importante de risco para as águas subterrâneas na exploração de gás de xisto. Uma metodologia é apresentada para avaliar a separação vertical entre diferentes pares de aquíferos e blocos de xisto presentes em toda a Inglaterra e País de Gales. A aplicação do método é feita em dois pares­o Aquífero do Grupo Cretáceo Chalk com a Formação Argilosa do Jurássico Superior Kimmeridge, e o Aquífero de Arenito Triássico com a Formação Xistosa do Carbonífero Bowland. Os desafios para definir o que pode ser considerado critérios de "separação segura" entre uma formação de gás de xisto e um aquífero sobrejacente são discutidos, em particular no que diz respeito a incertezas em propriedades geológicas, extensões de aquíferos e determinação de níveis de risco socialmente aceitáveis. As separações verticais modeladas sugerem que o risco de contaminação do aquífero por exploração de xisto variará muito entre os pares de xisto­aquífero e suas regiões, devendo assim serem consideradas cuidadosamente como parte da avaliação e gerenciamento de risco para qualquer desenvolvimento de gás de xisto.

Optimising implementation of a patient-assessment framework for emergency nurses: A mixed-method study.

AIMS AND OBJECTIVES: To determine potential facilitators and barriers and tailor interventions to optimise future implementation of a patient-assessment framework into emergency nursing practice. BACKGROUND: An evidence-informed patient-assessment framework HIRAID (History, Identify Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) improves the quality of patient assessments performed by emergency nurses. Facilitators and barriers must be understood and tailored interventions selected to optimise implementation. DESIGN: A mixed-method convergent study design was used. METHODS: Thirty eight early career emergency nurses from five Australian hospitals participated in an education workshop on the HIRAID assessment framework. Simulated clinical scenarios enabled participants to experience conducting a patient assessment with and without using the framework. All participants completed surveys, interviews and focus groups to identify potential facilitators and barriers. Twenty three participants completed follow-up telephone surveys 4-6 months later. Quantitative and qualitative data were analysed separately using descriptive statistics and inductive content analysis, prior to integration. Implementation interventions were selected using the Behaviour Change Wheel. RESULTS: Nine facilitators and nine barriers were identified to potentially effect implementation of the HIRAID assessment framework. Twelve of the 23 participants (52.2%) who completed follow-up surveys reported using the framework in the clinical setting. To optimise future implementation, the education workshop needs refinement, and environmental restructuring, modelling and social support are required. CONCLUSION: A multimodal strategy is needed to promote future successful implementation of the HIRAID assessment framework into emergency nursing practice. RELEVANCE FOR CLINICAL PRACTICE: The successful implementation of the HIRAID assessment framework has the potential to improve nursing assessments of patients in emergency and other acute care settings. This study demonstrates how to systematically identify facilitators and barriers to behaviour change and select interventions to optimise implementation of evidence-informed nursing practices.

The Evolving Role of Pathology in New Developments, Classification, Terminology, and Diagnosis of Pancreatobiliary Neoplasms.

Pancreatobiliary tract lesions are increasingly being discovered because of more sensitive imaging modalities. Magnetic resonance imaging has identified incidental pancreatic cysts in 13.5% of patients of progressively increasing age. Pancreatobiliary tissue is more accessible through endoscopic ultrasound and magnetic resonance imaging-guided biopsy procedures, and is now an integral part of pathologists' routine practice. Accordingly, several new tumor categories have been recently recognized, including intraductal tubulopapillary neoplasm, a new addition to tumoral intraepithelial neoplasms. Other entities have been reclassified, including the recent transition to 2-tiered grading of preinvasive neoplasms, as well as new perspectives on the distinctive biologic behavior of oncocytic intraductal papillary mucinous neoplasms (IPMNs) compared with other IPMN subtypes. This has led to proposals for revised staging of virtually every segment of the pancreatobiliary tree, with theranostic markers becoming an integral part of workup. Ki-67 is now an integral part of the classification of neuroendocrine tumors, with new definitions of "high-grade neuroendocrine carcinoma." Although bile duct brushings have opened new avenues for diagnosis, their sensitivity remains low and often requires concomitant fluorescent in situ hybridization to better define ambiguous cases. Various molecular pathways have been elucidated for pancreatic cysts, including KRAS for ductal neoplasia, GNAS for intestinal IPMNs, RNF3 for mucinous cysts, and VHL for serous cystic neoplasms, all key players in diagnostic workup. Integration of these updates into our understanding of pancreatobiliary disease requires active engagement of pathologists for appropriate specimen triage, judicious interpretation of results, and incorporation into reporting and staging. They also provide exciting opportunities for targeted therapy.

Test-retest reproducibility of the Assessment of Motor and Process Skills for school-aged children with acquired brain injuries.

Background Persistent impairments resulting from childhood acquired brain injury (ABI) can impact performance of activities of daily living (ADL). Objective and reliable measures of ADL skills are required for treatment planning and research. Aim To evaluate test-retest reproducibility of the Assessment of Motor and Process Skills (AMPS) for children with ABI. Methods Twenty-eight children with ABI (mean age 11 years 7 months, SD 2 years 4 months; males = 11) were recruited. Two AMPS tasks were performed over two consecutive days, as per standardized AMPS procedures. Intraclass correlation coefficients (ICC; 2,1), standard error of measurement (SEM), smallest detectable difference (SDD), and 95% limits of agreement (Bland-Altman) were calculated. Results Test-retest reliability was fair to good for AMPS ADL motor (ICC 0.55) and ADL process (ICC 0.58) measures. The SEM was 0.36 and 0.34 logits for AMPS ADL motor and ADL process measures respectively. The SDD was 1.0 (motor) and 0.93 logits (process) measures. A learning effect was evident. Conclusion Test-retest reproducibility of the AMPS was fair to good for children with ABI, which is poorer than previously published data. Administration of the AMPS in an unfamiliar environment, fatigue, and the small time interval between testing sessions may have contributed to poorer results. The AMPS remains a useful measure of ADL, contributing to our understanding of task execution processes.

Impact of multi-modal web-based rehabilitation on occupational performance and upper limb outcomes: pilot randomized trial in children with acquired brain injuries.

AIMS: To determine whether the multi-modal web-based rehabilitation 'Move it to improve it' (Mitii) is more effective than wait list control (usual care) to improve occupational performance, upper limb function, and visual perception in children with acquired brain injury (ABI). METHOD: Fifty-eight randomly allocated children (53% males; mean age 11y 11mo, SD 2y 6mo; Manual Abilities Classification Scale equivalent I=32, II=24, III=2; mean Full-scale IQ 75.8, SD 16.2) received either 20 weeks of Mitii (n=29) or usual care (n=29). Mitii comprised upper limb, cognitive, visual perception, and gross motor tasks, recommended for 30 minutes per day, 6 days per week, over 20 weeks. Outcomes were the Assessment of Motor and Process Skills (AMPS), Melbourne Assessment of Unilateral Upper Limb Function, Jebsen-Taylor Test of Hand Function, Test of Visual Perceptual Skills, Assisting Hand Assessment (AHA), and Canadian Occupational Performance Measure. The primary comparison at 20 weeks between groups on the AMPS process and motor measures used generalized estimating equations. RESULTS: Groups were equivalent at baseline. Participants completed on average 17.6 hours (range 0-46h) of Mitii. There were no differences between groups on the primary outcome (AMPS process: estimated mean difference -0.1, 95% CI -0.3 to 0.2, p=0.589; and AMPS motor: estimated mean difference 0.2, 95% CI -0.1 to 0.5, p=0.192). There were no differences between groups on overall visual perception, upper limb, and occupational performance outcomes. INTERPRETATION: Mitii led to negligible changes on all primary and secondary outcomes compared with usual care. This likely reflects the small dose achieved and poses questions around the acceptability and feasibility of home-delivered Mitii in this population of children with ABI.

Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous neoplasm: Criteria and clinical implications of accurate diagnosis.

BACKGROUND: Cytologic findings of pancreatic oncocytic-type intraductal papillary mucinous neoplasms (IPMNs)/intraductal oncocytic papillary neoplasms (IOPNs) are largely unknown. METHODS: Five IOPNs encountered by the authors were analyzed. RESULTS: Four IOPNs were located in the pancreatic head, and 1 was located in the pancreatic body/tail in 2 men and 3 women ages 56 to 84 years (mean age, 66 years). Radiologic diagnoses included pancreatic ductal adenocarcinoma (PDAC) in 2 patients, invasive cancer associated with IPMN in 1 patient, IPMN versus mucinous cystic neoplasm in 1 patient, and cystic mass in 1 patient. Cytologic findings included: hypercellular smears (4 of 5 cases) containing well formed clusters of oncocytic cells (5 of 5 cases) with prominent, slightly eccentric nucleoli (4 of 5 cases), predominantly arranged in sheets/papillary units (5 of 5 cases), with punched-out intercytoplasmic spaces (4 of 5 cases), and with occasional 3-dimensional groups and focal necrosis (3 of 5 cases). The intracytoplasmic mucin and thick extracellular mucin typical of other IPMNs were observed only in 2 cases and were very limited. The mean size on resection was 4.5 cm. Invasion was observed in 3 cases (0.1, 0.3, and 2.0 cm) of tubular-type IPMN. Initial cytologic evaluation was performed by the authors in 4 of 5 cases, which were diagnosed as IOPN (n = 3) and IPMN versus cystic PDAC (n = 1). One case was initially misdiagnosed as PDAC and, on resection, proved to be noninvasive IOPN. CONCLUSIONS: Cytologic features of IOPNs are classical, similar to their histologic counterparts, and differ significantly from other IPMN subtypes. Because of their highly complex appearance, they are often radiologically misdiagnosed as PDAC; thus, failure to recognize their characteristic features on fine-needle aspiration may lead to inappropriate treatment. Patients with IOPN have an incomparably better prognosis than patients with ordinary PDAC, even when their neoplasms are invasive.

Mitii™ ABI: study protocol of a randomised controlled trial of a web-based multi-modal training program for children and adolescents with an Acquired Brain Injury (ABI).

BACKGROUND: Acquired brain injury (ABI) refers to multiple disabilities arising from damage to the brain acquired after birth. Children with an ABI may experience physical, cognitive, social and emotional-behavioural impairments which can impact their ability to participate in activities of daily living (ADL). Recent developments in technology have led to the emergence of internet-delivered therapy programs. "Move it to improve it" (Mitii™) is a web-based multi-modal therapy that comprises upper limb (UL) and cognitive training within the context of meaningful physical activity. The proposed study aims to compare the efficacy of Mitii™ to usual care to improve ADL motor and processing skills, gross motor capacity, UL and executive functioning in a randomised waitlist controlled trial. METHODS/DESIGN: Sixty independently ambulant children (30 in each group) at least 12 months post ABI will be recruited to participate in this trial. Children will be matched in pairs at baseline and randomly allocated to receive either 20 weeks of Mitii™ training (30 min per day, six days a week, with a potential total dose of 60 h) immediately, or be waitlisted for 20 weeks. Outcomes will be assessed at baseline, immediately post-intervention and at 20 weeks post-intervention. The primary outcomes will be the Assessment of Motor and Process Skills and 30 s repetition maximum of functional strength exercises (sit-to-stand, step-ups and half kneel to stand). Measures of body structure and functions, activity, participation and quality of life will assess the efficacy of Mitii™ across all domains of the International Classification of Functioning, Disability and Health framework. A subset of children will undertake three tesla (3T) magnetic resonance imaging scans to evaluate functional neurovascular changes, structural imaging, diffusion imaging and resting state functional connectivity before and after intervention. DISCUSSION: Mitii™ provides an alternative approach to deliver intensive therapy for children with an ABI in the convenience of the home environment. If Mitii™ is found to be effective, it may offer an accessible and inexpensive intervention option to increase therapy dose. TRIAL REGISTRATION: ANZCTR12613000403730.

Hybrid push-pull endoscopic and laparoscopic full thickness resection for the minimally invasive management of gastrointestinal stromal tumors: a pilot clinical study.

Background. Gastric gastrointestinal stromal tumors (GISTs) that are predominantly endophytic or in anatomically complex locations pose a challenge for laparoscopic wedge resection; however, endoscopic resection can be associated with a positive deep margin given the fourth-layer origin of the tumors. Methods. Patients at two tertiary care academic medical centers with gastric GISTs in difficult anatomic locations or with a predominant endophytic component were considered for enrollment. Preoperative esophagogastroduodenoscopy (EGD), endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA), and cross-sectional imaging were performed. Eligible patients were offered and consented for hybrid and standard management. Results. Over ten months, four patients in two institutions with anatomically complex or endophytic GISTs underwent successful, uncomplicated push-pull hybrid procedures. GIST was confirmed in all resection specimens. Conclusion. In a highly selected population, the hybrid push-pull approach was safe and effective in the removal of complex gastric GISTs. Endoscopic resection alone was associated with a positive deep margin, which the push-pull technique manages with a laparoscopic, full thickness, R0 resection. This novel, minimally invasive, hybrid laparoscopic and endoscopic push-pull technique is a safe and feasible alternative in the management of select GISTs that are not amenable to standard laparoscopic resection.

Testicular tumors: what radiologists need to know--differential diagnosis, staging, and management.

Cryptorchidism, family history, and infertility are risk factors for testicular cancer. Most testicular cancers occur in young men aged 18-35 years, and seminoma is the most common cell type. Testicular tumors are usually diagnosed at ultrasonography (US) and are staged at computed tomography (CT) or magnetic resonance (MR) imaging. At US, testicular tumors usually appear as a solid intratesticular mass. Because the differential diagnosis includes infarct and infection, correlation with patient history and symptoms is important. At staging CT or MR imaging, retroperitoneal lymph nodes are considered regional lymph nodes, and the greatest nodal diameter is used to distinguish among N1-N3 disease. The right testicular vein drains into the inferior vena cava, and the left testicular vein drains into the left renal vein. Because of venous and lymphatic drainage pathways, retroperitoneal lymph nodes are the initial landing station for testicular cancers. Enlarged lymph nodes in the supraclavicular region, chest, and pelvis are considered distant metastases. Testicular cancer is initially treated with orchiectomy. The patient may then undergo active surveillance, chemotherapy, radiation therapy, or retroperitoneal lymph node resection, depending primarily on the clinical stage. Radiologists play an important role in initial diagnosis, staging, and imaging surveillance of testicular malignancies.

Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma.

OBJECTIVES: Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. METHODS: In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. CONCLUSIONS: A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.

Chemoprevention of head and neck cancer with celecoxib and erlotinib: results of a phase ib and pharmacokinetic study.

Epidermal growth factor receptor (EGFR) and COX-2 inhibitors synergistically inhibit head and neck squamous cell carcinoma tumorigenesis in preclinical studies. We conducted a phase I and pharmacokinetic study with the erlotinib and celecoxib combination in patients with advanced premalignant lesions. Thirty-six subjects with oral leukoplakia, mild, moderate, or severe dysplasia, or carcinoma in situ were screened for study participation; 12 consented and received therapy for a median of 5.38 months. Erlotinib was escalated following a standard 3+3 design at 50, 75, and 100 mg orally daily and celecoxib was fixed at 400 mg twice daily for 6 months. Biopsy of lesions and cytobrush of normal mucosa were performed at baseline, 3, 6, and 12 months. Erlotinib pharmacokinetics were analyzed in 10 subjects. The maximum tolerated dose of erlotinib with celecoxib 400 mg BID was 50 mg per day with skin rash being the main observed toxicity. Overall histologic response rate was 63% (complete response, 43%; partial response, 14%; stable disease, 29%; and disease progression, 14%). With median follow-up of 36 months, mean time to progression to higher-grade dysplasia or carcinoma was 25.4 months. Downregulation of EGFR and p-ERK in follow-up biopsies correlated with response to treatment. Larger average erlotinib V/F (approximately 308 L) and CL/F (8.3 L/h) compared with previous studies may be related to relatively large average bodyweights. Average erlotinib t1/2 was 25.6 hours. Encouraging responses to the celecoxib and erlotinib combination correlated with EGFR pathway inhibition. Although erlotinib-related rash was the main limitation to dose escalation, the intervention was well tolerated.

Health resource utilization and multidisciplinary impact of endoscopic ultrasonography in a tertiary referral medical center.

BACKGROUND: Endoscopic ultrasound (EUS) is a resource-intensive endoscopic procedure, but may result in high downstream health resource utilization and multispecialty impact. Our aim was to examine the downstream impact of EUS by specialty and by indication. METHODS: A retrospective chart review was performed at an academic medical center for patients for whom EUS represented the first point of contact at the study institution within a 20-month period. RESULTS: A total of 552 EUS procedures were reviewed and 208 represented the first point of contact. The most common principle indication involved the pancreas (n = 117, 56%). Downstream health utilization was calculated for an average of 313 days postprocedure (range: 35-632 days). Following unique referral for endoscopic ultrasound, 52% of the patients in the study were retained within the institution for further management and, of these, 34% had a major intervention in the form of surgery or chemoradiotherapy. Compared with other indications, patients presenting with a pancreatic mass were significantly more likely to remain in the study institution for further management (62% versus 39%, p = 0.005), were more likely to have a downstream surgery (29% versus 14%, p = 0.020) and were more likely to have downstream chemo-radiotherapy (11% versus 3%, p = 0.012). CONCLUSIONS: EUS represents a unique portal of entry into tertiary referral medical centers. First point of contact EUS referrals are associated with major downstream health resource utilization and significantly increased utilization for mass lesions of the pancreas.

Educating Australian registered nurses in comprehensive health assessment: a pilot study.

BACKGROUND: Physical and mental health problems are interconnected, and registered nurses need to be competent in performing comprehensive physical and mental health assessment. This article reports on a pilot evaluation of education in comprehensive health assessment and clinical judgment for registered nurses enrolled in a master of nursing program. METHODS: Observation and interview data were collected from nine teaching staff and students. RESULTS: Analysis resulted in three themes: reconstructing specialty knowledge, integrating revised knowledge into practice, and expanding practice. Students and staff navigated a process of deconstructing existing specialty knowledge and reconstructing knowledge to incorporate a revised understanding of comprehensive assessment. Although there were barriers to implementing this process in practice, students reported that their extended understanding expanded their assessment practices and influenced some colleagues' practices. CONCLUSION: There is a need for continuing education in comprehensive health assessment for registered nurses as well as investigation of the translation of this knowledge into practice.

Chemoprevention of head and neck cancer by simultaneous blocking of epidermal growth factor receptor and cyclooxygenase-2 signaling pathways: preclinical and clinical studies.

PURPOSE: We investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I). EXPERIMENTAL DESIGN: We examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib. RESULTS: The combined treatment inhibited head and neck cancer cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell-cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK, and pS6 levels after treatment, which correlated with clinical response. CONCLUSION: Treatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. Clin Cancer Res; 19(5); 1244-56. ©2013 AACR.

Increased diagnostic yield of endoscopic ultrasound-guided fine needle aspirates with flow cytometry and immunohistochemistry.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most sensitive and specific test for establishing a tissue diagnosis for many gastrointestinal malignancies; however, cytologic morphology alone may not be definitive for subsets of tumors. Our aim was to quantify the impact of the broad application of flow cytometry (FC) and immunohistochemistry (IHC) on EUS-FNA diagnostic yield. A retrospective chart review was performed on EUS procedures at a tertiary referral, academic medical center. All EUS-FNA cases performed over a 21-month period were examined. Of 606 EUS procedures reviewed during the period of study, 264 utilized FNA. After pancreatic cyst cases were excluded, 235 EUS-FNA cases for 221 patients were selected for analysis. For cases with subsequent histological evaluation, including the subset utilizing FC/IHC, the sensitivity of EUS-FNA was 89%, specificity was 100%, and accuracy was 91%. One quarter (58/235, 25%) of the tissue specimens underwent further testing by FC/IHC. There were 48 definitive diagnoses made in the subset utilizing FC/IHC. In 20 of the 48 diagnoses (42%), FC/IHC was deemed critical to the diagnosis, and without FC/IHC testing in those cases, the overall sensitivity and accuracy of EUS-FNA would be reduced to 74 and 77%, respectively. FC/IHC allowed for six diagnoses rarely or not previously described by EUS-FNA. Application of FC/IHC improves characterization predominantly for nonadenocarcinoma tumor subtypes and may lead to a diagnostic result for tumors not previously characterized by EUS-FNA. With an adequate tissue sample, broad application of FC/IHC increases the diagnostic yield of EUS-FNA.