Surgical Management of Lymph Nodes in Melanoma.

This article provides a comprehensive evaluation of surgical management of the lymph node basin in melanoma, with historical, anatomic, and evidence-based recommendations for practice.

Radical chest wall resection and hyperfractionated accelerated radiotherapy for radiation-associated angiosarcoma of the breast: A safe and effective treatment strategy.

Radiation-associated angiosarcomas (RAS) of the breast are vascular tumors arising in a previous radiation field for primary breast cancer. They occur rarely but confer a high probability of local recurrence (LR) and poor prognosis. A wide range of treatment strategies exists due to limited evidence, and although resection is the definitive treatment, LR rates remain high. It has been suggested hyperfractionated accelerated radiotherapy (HART) has the potential to prevent LR. The sarcoma group at the Juravinski Cancer Centre (JCC) reports our experience of nine patients treated with radical resection and adjuvant HART. This is one of the largest reported cohorts we are aware of to receive this treatment. The JCC pathologic data base was reviewed between the year 2006-2015 for patients with RAS. Patients who received radical surgery and immediate HART were eligible. Patients underwent radical chest wall resection and en bloc mastectomy. Radiotherapy was then delivered to 4500 cGy in 45 fractions three times daily using parallel opposed photon beams and electron patching, or volumetric modulated arc therapy. Primary outcome was recurrence-free survival in months, and records were reviewed for descriptive reports of toxicity. We compared our results to other institutions experience with surgery alone or other adjuvant therapies. Median follow-up was 19 months (range 3-41 months). One of nine patients developed LR and developed metastasis, one died of other causes, and seven are alive with no recurrent disease. There were seven reports of mild skin toxicity during treatment. One patient developed chronic wound healing complications which eventually resolved and one patient developed asymptomatic radiation osteitis of a rib. On the basis of our experience at the JCC, we recommend treatment with radical chest wall resection and adjuvant HART to prevent recurrence in RAS patients. As demonstrated in our patients, the large normal tissue volume irradiated is tolerable with in combination with small fraction sizes, and no major toxicities were seen. Further investigation into adjuvant therapy regimens and prospective studies are required to reach consensus on optimal treatment for this disease.

Predictors of 5-year local, regional, and distant recurrent events in a population-based cohort of breast cancer patients.

BACKGROUND: The study purpose was to identify tumor and surgeon predictors of local recurrence (LR), regional recurrence (RR), and distant metastasis (DM) after breast cancer (BC) surgery in a population-based cohort. METHODS: Consecutive BC surgical cases from 12 hospitals in South Central Ontario between May 2006 and October 2006 were included. Data collected on chart review included patient and tumor factors, surgery type, adjuvant treatment, surgeon specialty, surgeon case volume, and practice type. Univariate and multivariable survival analyses were performed. RESULTS: Median follow-up was 5.5 years for 402 patients (97% of sample). LR, RR, and DM occurred in 18 (4.5%), 10 (2.5%), and 47 (12%) patients, respectively. Significant predictors of BC recurrence (LR or RR or DM) were tumor size and grade, nodal status, and lymphovascular invasion on multivariable analysis. CONCLUSION: Tumor factors such as size, grade, lymphovascular invasion, and nodal status predicted BC recurrence, while practice type, surgeon specialty, and case volume did not.

Barriers, beliefs and practice patterns for breast cancer reconstruction: A provincial survey.

BACKGROUND: The purpose of this study was to characterize beliefs and practice patterns for breast cancer reconstruction among physicians who treat patients with breast cancer, in order to delineate current clinical practice. This survey was administered prior to Cancer Care Ontario guideline publication. METHOD: Survey questions addressed four domains: survival, delayed or obscured recurrence detection, delayed adjuvant therapy, and aesthetics. The survey was administered to 1160 Ontario plastic and general surgeons and radiation and medical oncologists. Data were compared to published guidelines. RESULTS: The overall response rate was 48%, with 57% of respondents treating breast cancer. Of those treating breast cancer, 75% are affiliated with an academic center. Immediate breast reconstruction (IBR) is not available to 28%. Autologous reconstruction is thought to interfere with recurrence detection by 23% (oncologists 30%, surgeons 19%, p = 0.04). For patients not expected to require radiation therapy, IBR is not supported by 30%. Autologous IBR is believed to delay delivery of adjuvant chemotherapy by 45% (oncologists 55%, surgeons 41%, p = 0.02). Up to 42% of respondents believe delays in adjuvant therapy delivery following IBR are due to insufficient health care resources (ie. coordinating an oncologic and reconstructive surgeon). Radiation therapy following reconstruction is believed to have negative aesthetic outcomes, and increase the need for revision surgery. CONCLUSIONS: Unfavourable beliefs about certain clinical actions do not align with recent provincial guideline recommendations. Insufficient healthcare resources are perceived to be a significant barrier to IBR and timely care.

Results of a surgeon-directed quality improvement project on breast cancer surgery outcomes in South-Central Ontario.

BACKGROUND: Gaps in breast cancer (BC) surgical care have been identified. We have completed a surgeon-directed, iterative project to improve the quality of BC surgery in South-Central Ontario. METHODS: Surgeons performing BC surgery in a single Ontario health region were invited to participate. Interventions included: audit and feedback (A&F) of surgeon-selected quality indicators (QIs), workshops, and tailoring interviews. Workshops and A&F occurred yearly from 2005-2012. QIs included: preoperative imaging; preoperative core biopsy; positive margin rates; specimen orientation labeling; intraoperative specimen radiography of nonpalpable lesions; T1/T2 mastectomy rates; reoperation for positive margins; sentinel lymph node biopsy (SLNB) rates, number of sentinel lymph nodes; and days to receive pathology report. Semistructured tailoring interviews were conducted to identify facilitators and barriers to improved quality. All results were disseminated to all surgeons performing breast surgery in the study region. RESULTS: Over 6 time periods, 1,828 BC charts were reviewed from 12 hospitals (8 community and 4 academic). Twenty-two to 40 participants attended each workshop. Sustained improvement in rates of positive margins, preoperative core biopsies, specimen orientation labeling, and SLNB were seen. Mastectomy rates and overall axillary staging rates did not change, whereas time to receive pathology report increased. The tailoring interviews concerning positive margins, SLNB, and reoperation for positive margins identified facilitators and barriers relevant to surgeons. CONCLUSIONS: This surgeon-directed, regional project resulted in meaningful improvement in numerous QIs. There was consistent and sustained participation by surgeons, highlighting the importance of integrating the clinicians in a long-term, iterative quality improvement strategy in BC surgery.

The implementation of a surgeon-directed quality improvement strategy in breast cancer surgery.

BACKGROUND: The investigators designed a sustained, surgeon-directed, iterative project to improve the quality of breast cancer surgery in south central Ontario. METHODS: The strategy included audit and feedback of surgeon-selected quality indicators, workshops, and tailoring interviews. Workshops were held to discuss quality improvement strategies, select quality indicators, review audited results, and select interventions for subsequent implementation. Semistructured tailoring interviews were conducted to identify facilitators and barriers to improved quality. All presentations and results were disseminated to all surgeons performing breast surgery in the study region. RESULTS: Forty-four surgeons performing breast surgery across 12 hospitals are involved in the project. Five workshops have been held since 2005. Surgeons' enthusiasm and involvement in the project have been positive. Interim results demonstrated that over 4 audit cycles (2006-2010), the preoperative core biopsy rate increased from 73% to 92%. The tailoring interviews indicated that 18 of 21 surgeons performed preoperative core biopsies. CONCLUSIONS: This project highlights the feasibility of a surgeon-directed, iterative quality improvement strategy in breast cancer surgery. Interim results demonstrate consistent improvements in a key selected quality indicator.

An evaluation of intraoperative digital specimen mammography versus conventional specimen radiography for the excision of nonpalpable breast lesions.

BACKGROUND: This study examined the impact of intraoperative digital specimen mammography (IDSM) compared with conventional specimen radiography (CSR) for nonpalpable breast lesions in patients undergoing breast-conserving surgery (BCS). METHODS: In this retrospective cohort study, 201 consecutive image-detected nonpalpable breast lesions underwent BCS after preoperative localization and specimen radiography. Data on patient, tumor, and surgical factors were collected. RESULTS: CSR was performed in 105 patients and IDSM was used in 96 patients. Patient and tumor factors were similar in both groups. Using univariate analysis, CSR resulted in more positive margins (19% vs 6.2%; P = .012). Rates of cavity margin resection, reoperation, and operative times were similar for CSR and IDSM. Independent predictors of positive margins on multivariable analysis were use of CSR, microcalcifications on mammography, the need for bracketing for localization, and no cavity margin excision (all P < .05). CONCLUSIONS: In this study, the use of IDSM resulted in fewer positive margins after BCS, although operative times were similar.

Primary tumor and patient characteristics in breast cancer as predictors of adjuvant therapy regimen: a regression model.

PURPOSE: Adjuvant therapy reduces the risk of recurrence of breast cancer. This study was undertaken to determine characteristics guiding choice of adjuvant therapy. METHODS: A retrospective review was completed of characteristics of patients with breast cancer (stages I-III) at a regional center from 2004 to 2007. Univariate analysis was used to select factors (P < 0.1) for entry into multivariate stepwise logistic regressions. Odds ratios with 95% confidence intervals were calculated. A P value of <0.05 was significant, and comparisons were two-tailed. RESULTS: Model 1 (n = 744) assessed the prescription of any adjuvant regimen (hormonal or chemotherapy). Indicators of choice of any regimen were positive lymph nodes [OR 16.5, CI (6.2, 44.0)], grade [4.0, (2.5, 6.0)], size [3.2, (2.1, 4.6)], PR [0.3, (0.1, 0.6)], and multicentricity [0.2 (0.04, 0.66)]. Model 2 (n = 663) assessed chemotherapy in ER+ patients. Indicators of addition of chemotherapy were stage [8.9 (4.3, 18.6), grade [5.5 (3.1, 9.6)], positive nodes [2.7 (1.1, 6.4)], physician experience [1.1 (1.0, 1.2)], age [0.8 (0.79, 0.86)], and year of treatment [0.8, (0.4, 0.9)]. Model 3 (n = 867) assessed prescription of a more aggressive chemotherapy regimen and indicators were treatment by a breast specialist oncologist [8.6 (1.7, 43.1)], stage [3.6 (2.4, 5.4)], positive nodes [2.6 (1.7, 4.1)], year of treatment [1.5 (1.3, 1.8)], size [1.2 (1.1, 1.4)], age [0.91 (0.89, 0.93)], and PR [0.4 (0.3, 0.6)]. CONCLUSIONS: This study verifies known factors for choice of adjuvant therapy, excludes others thought to be important, and quantifies effects at our center. Further studies are required to compare these models where risk stratification is different.

Asymmetric synthesis of axially chiral 1-aryl-5,6,7,8-tetrahydroquinolines by cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction of 1-aryl-1,7-octadiynes and nitriles.

The asymmetric synthesis of a range of axially chiral 2-arylpyridines by a cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction is described. The use of a planar chiral (1-neomenthylindenyl)cobalt(COD) complex under photochemical conditions is the key for reacting the 1-naphthyldiynes with a range of differently functionalized nitriles, giving the enantiomeric atropoisomers with high chemical yields and enantiomeric excesses of up to 94% ee.

The fascinating construction of pyridine ring systems by transition metal-catalysed [2 + 2 + 2] cycloaddition reactions.

Cycloaddition reactions compose one of the most important classes of reactions when it comes to the simultaneous formation of several bonds in one reaction step. The de novo construction of carbocyclic aromatic systems from acetylenes was also found as an excellent possibility for the assembly of heteroaromatic systems. The transition metal-catalysed [2 + 2 + 2] cycloaddition reaction constitutes a fascinating tool for the synthesis of pyridines from nitriles and the most recent developments demonstrate the ability to control the substitution pattern as well as the possibility of introducing chirality by the use of achiral substrates and a chiral catalyst under mild conditions. In this tutorial review we are focusing on the de novo construction of pyridine ring systems by the transition metal-catalysed [2 + 2 + 2] cycloaddition reaction. After surveying the mechanistic features and intermediates of the reaction depending on the different metal complexes used, we depict the preparation of achiral pyridine derivatives. The last section describes the advances in the synthesis of chiral pyridines and biaryls using the cyclotrimerization method. The various possibilities of introducing chirality by catalytic means are presented and illustrated by instructive examples. This review will be of interest for people active in: Organic Chemistry, Organometallic Chemistry, Transition Metal Chemistry, Stereoselective Synthesis, Heterocyclic Chemistry.

Preparation of new axially chiral bridged 2,2'-bipyridines and pyridyl monooxazolines (pymox). Evaluation in copper(I)-catalyzed enantioselective cyclopropanation.

This work reports the synthesis of new axially chiral bridged 2,2'-bipyridines 1 and pyridylmonooxazolines (pymox) 2. The potential of these new axially chiral N,N-ligands was evaluated in asymmetric catalytic cyclopropanation of styrene derivatives 22a-c with diazoesters 21a,b. While 2,2'-bipyridines 1a-c afforded the corresponding cyclopropanes 23a-f in up to 65% ee, pymoxs 2a-e gave somewhat lower enantioselectivities (up to 53% ee). Both classes of ligands produced trans-cyclopropanes 23a-f as the major isomer, although with modest diasteroselectivities (56 : 44 to 78 : 22). A structure-stereoselectivity relationship study of ligands 1 and 2 identified the chiral biaryl axis as being mostly responsible for the enantioselective performances of these ligands.

Phosphorus-bearing axially chiral biaryls by catalytic asymmetric cross-cyclotrimerization and a first application in asymmetric hydrosilylation.

A novel and efficient, two-step route to axially chiral biaryls is demonstrated. In a direct asymmetric cross-cyclotrimerization in the presence of a chiral cobalt(I) catalyst, axially chiral biaryls bearing phosphoryl moieties have been prepared, and through indirect evidence the authors have been able to clarify the origin of the stereochemical induction and the nature of the central intermediate in the catalytic cycle. By subsequent reduction of the phosphoryl moiety to the corresponding phosphine, a very efficient and atom-economical approach to chiral systems has been developed. These chiral systems clearly have great potential use as axially chiral monodentate P- or bidentate P,O-ligands, as has been demonstrated by the employment of the novel NAPHEP as a new monodentate acting ligand in an asymmetric hydrosilylation reaction.

Adaptive guideline-based treatment workflows with AdaptFlow.

One goal in modern medicine is to increase the treatment quality. A major step towards this aim is to support the execution of standardized, guideline-based clinical protocols, which are used in many medical domains, e.g., for oncological chemotherapies. Standardized chemotherapy protocols contain detailed and structured therapy plans describing the single therapy steps (e.g., examinations or drug applications). Therefore, workflow management systems offer good support for these processes. However, the treatment of a particular patient often requires modifications due to unexpected infections, toxicities, or social factors. The modifications are described in the treatment protocol but not as part of the standard process. To be able to further execute the therapy workflows in case of exceptions running workflows have to be adapted dynamically. Furthermore, the physician should be supported by automated exception detection and decision support for derivation of necessary modifications. The AdaptFlow prototype offers the required support for the field of oncological chemotherapies by enhancing a workflow system with dynamic workflow adaptation and rule based decision support for exception detection and handling.

Educating nurses for leadership roles.

As a result of the growing shortage of nurses and the dramatically changing role of the front-line nurse manager, leadership education for nurses is of critical importance. The purpose of the project described in this article was to design, implement, and evaluate an innovative model of nursing leadership development for students enrolled in registered nurse to bachelor of science in nursing or registered nurse to master of science in nursing programs. A guided "action-learning" course was designed that focused on both core knowledge and experiential learning. The course was developed with the assistance of an advisory panel of prominent nurse leaders with expertise in administration, health policy, informatics, and nursing education. The prototype course was offered for the first time as an elective in Spring 2003. Evaluation data indicated that the course was considered valuable by students and with modifications suggested by students, faculty, and advisory panel members, the course would be offered regularly as part of the curriculum. Recommendations also included adapting course content to a continuing education format.

Oxaprozin versus diclofenac in NSAID-refractory periarthritis pain of the shoulder.

OBJECTIVE: To evaluate the efficacy and safety of oxaprozin in comparison with diclofenac in patients with periarthritis pain of the shoulder previously unsuccessfully treated with nonsteroidal anti-inflammatory drugs other than diclofenac and oxaprozin. METHODS: In this open, multicentre, randomised, controlled study, eligible patients with periarthritis of the shoulder were randomised to receive either oxaprozin 1200 mg once daily (n = 49) or diclofenac 50 mg three times daily (n = 47). The treatment period was 15 +/- 1 days. The study was planned on a hypothesis of equivalence between the two study drugs. The primary study endpoint was the change from baseline at day 15 in the patient-assessed shoulder pain score. Secondary efficacy variables included investigator-assessed shoulder function, patient-assessed quality of life on the Short-Form-36 (SF-36) Acute Health Survey and both patients' and investigators' overall assessment of efficacy. RESULTS: At day 15, the mean changes in shoulder pain score from baseline in the oxaprozin and diclofenac groups were -5.85 +/- SD 4.62 and -5.54 +/- SD 4.41, respectively. The difference between the two groups was not statistically significant, confirming the hypothesis of the study that oxaprozin is as effective as diclofenac. Investigator-assessed shoulder function improved in both groups but more so in the oxaprozin group (p = 0.028 at day 15). Quality of life as measured by SF-36 total score was also improved in both treatment groups, with a trend toward greater improvement in the oxaprozin group. Furthermore, a significantly more favourable effect on the SF-36 'mental health' item was observed in oxaprozin compared with diclofenac-treated patients at day 15 (p = 0.0202). As assessed by investigators, the overall efficacy of oxaprozin was superior to that for diclofenac at visit 3 (8 +/- 1 days) (p = 0.0067). Patients also assessed the overall efficacy of oxaprozin as superior to that of diclofenac at visits 3 (8 +/- 1 days) (p = 0.0235) and 4 (15 +/- 1 days) (p = 0.0272). Only six adverse events, all of which were mild or moderate in intensity and occurred in four diclofenac recipients, were observed in the study. CONCLUSIONS: As expected, once-daily oxaprozin proved to be as effective as diclofenac three times daily in reducing the primary efficacy variable of patient-assessed shoulder pain score in patients with periarthritis of the shoulder refractory to previous treatments with other NSAIDs. Oxaprozin was shown to be superior to diclofenac in improving shoulder function and was considered by investigators and patients to have greater overall efficacy than diclofenac. In addition, oxaprozin showed a trend toward superior results in improving patients' quality of life compared with diclofenac. A trend towards better tolerability results for oxaprozin compared with diclofenac was also noted.

Induction of protective immunity against lethal anthrax challenge with a patch.

BACKGROUND: Transcutaneous immunization (TCI) is a needle-free technique that delivers antigens and adjuvants to potent epidermal immune cells. To address critical unmet needs in biodefense against anthrax, we have designed a novel vaccine delivery system using a dry adhesive patch that simplifies administration and improves tolerability of a subunit anthrax vaccine. METHODS: Mice and rabbits were vaccinated with recombinant protective antigen of Bacillus anthracis and the heat-labile toxin of Escherichia coli. Serologic changes, levels of toxin-neutralizing antibodies (TNAs), and pulmonary and nodal responses were monitored in the mice. A lethal aerosolized B. anthracis challenge model was used in A/J mice, to demonstrate efficacy. RESULTS: The level of systemic immunity and protection induced by TCI was comparable to that induced by intramuscular vaccination, and peak immunity could be achieved with only 2 doses. The addition of adjuvant in the patch induced superior TNA levels, compared with injected vaccination. CONCLUSIONS: Anthrax vaccine patches stimulated robust and functional immune responses that protected against lethal challenge. Demonstration of responses in the lung suggests that a mechanism exists for protection against challenge with aerosolized anthrax spores. A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.

The Governor's Wellmobile: Maryland's mobile primary care clinic.

This article describes the development and implementation of the Governor's Wellmobile program. Designed to increase access to community-based health care for uninsured, underserved populations and to provide innovative clinical practice, research, and education opportunities for students and faculty, this fleet of four full-service, primary care clinics "on wheels" is managed and operated by the University of Maryland School of Nursing, demonstrating that nurse-managed practice models are valuable to the state's health care delivery system. Issues of long-term financial sustainability are presented, as well as lessons learned about the importance of public, private, and philanthropic partnerships and political support in ensuring the success of such programs.

Addressing the shortage. Strategies for building the nursing workforce.

For more than two decades, nursing educators and administrators have grappled with issues of declining student enrollments and the concurrent "defection" of nurses from the labor market. This article describes both short- and long-term strategies for addressing the nursing shortage and identifies new opportunities for collaboration in building the nursing workforce of the future.

Facile and racemization-free conversion of chiral nitriles into pyridine derivatives.

The results described herein demonstrate how the very mild reaction conditions of the Co(I)-catalyzed photochemical [2 + 2 + 2] cyclocotrimerization are suited to prepare chiral compounds containing unsubstituted and polysubstituted 2-pyridyl moieties starting from chiral nitriles without any detectable loss of enantiomerical purity. This further increases the already very broad synthetic scope of this particular reaction.