Code status communication training in postgraduate oncology programs: a needs assessment.

Background: Discussions with patients with cancer about cardiopulmonary resuscitation directives (code status) are often led by residents. This study was carried out in Canada to identify current educational practices and gaps in training for this communication skill. Methods: Canadian medical and radiation oncology residents and program directors (pds) were surveyed about teaching practices, satisfaction with current education, and barriers to teaching code status discussion skills. Relative frequencies of categorical and ordinal responses were calculated. Results: Between November 2016 and February 2017, 95 (58.6%) of 162 residents and 17 (63%) of 27 pds completed surveys. Only 54.1% and 48.3% of medical and radiation oncology residents, respectively, had received any code status communication training before entering an oncology program. While 41% of residents expected to receive formal teaching on this topic during residency, 47.1% of pds endorsed inclusion of this topic in curricula. Only 20% of residents reported receiving formal evaluation of this skill while 41.2% of pds indicated that evaluations are provided. The importance of this communication skill in oncology was strongly supported. Among residents, 88% desired more training, and 82.3% of pds identified the need for new educational resources. Lack of time, resources, and evaluation tools were among the most commonly identified barriers to teaching. Conclusions: Oncology residency pds and trainees feel that code status communication is important, but teaching and evaluation of this skill are limited. Barriers to teaching and skill-building have been identified. Further work is underway to develop novel educational resources for code status communication training.

An evaluation of the safety of continuing trastuzumab despite overt left ventricular dysfunction.

Background: The major limitation in the use of trastuzumab therapy is cardiotoxicity. We evaluated the safety of a strategy of continuing trastuzumab in patients with breast cancer despite mild, asymptomatic left ventricular impairment. Methods: Charts of consecutive patients referred to a cardio-oncology clinic from January 2015 to March 2017 for decline in left ventricular ejection fraction (lvef), defined as a fall of 10 percentage points or more, or a value of less than 50% during trastuzumab therapy, were reviewed. The primary outcome of interest was change in lvef, measured before and during trastuzumab exposure and up to 3 times after initiation of cardiac medications during a median of 9 months. Results: All 18 patients referred for decline in lvef chose to remain on trastuzumab and were included. All patients were treated with angiotensin converting-enzyme inhibitors or beta-blockers, or both. After initiation of cardiac medications, lvef increased over time by 4.6 percentage points (95% confidence interval: 1.9 percentage points to 7.4 percentage points), approaching baseline values. Of the 18 patients, 17 (94%) were asymptomatic at all future visits. No deaths occurred in the group. Conclusions: Many patients with mildly reduced lvef and minimal heart failure symptoms might be able to continue trastuzumab without further decline in lvef, adverse cardiac events, or death when treated under the supervision of a cardiologist with close follow-up.

MEDiastinal Irradiation and CArdio-Toxic Effects (MEDICATE): Exploring the Relationship between Cardiac Irradiation and High Sensitivity Troponins.

AIMS: Radiation-induced heart disease is a late effect of cardiac irradiation and has been shown in patients with lymphoma and thoracic cancers. There is no established measurement tool to detect acute cardiac damage. However, high sensitivity troponin I and T (HsTnI and HsTnT) and echocardiograms have shown promise in some studies. A pilot trial was conducted to characterise whether these instruments may detect subclinical radiotherapy-induced cardiac damage. MATERIALS AND METHODS: Eligible patients received high cardiac doses defined by either at least 30 Gy to 5% of cardiac volume or a mean dose of 4 Gy. HsTnI and HsTnT were measured before radiotherapy and after 2 and 4 weeks of radiotherapy; three-dimensional echocardiograms were completed before and 1 year after radiotherapy. RESULTS: Of 19 patients, the median 'mean left ventricular dose' was 3.1 Gy and the 'mean cardiac dose' was 8.6 Gy. Significant positive associations between HsTnI and HsTnT were observed at all time points, but there was no significant association with cardiac dose. The mean left ventricular dose and the maximum left ventricular dose were, however, associated with a decrease in ejection fraction (P = 0.054, 0.043) as well as an increase in left ventricular strain (P = 0.058). CONCLUSION: This study suggests that HsTnI and HsTnT are intimately related, but detection of acute cardiac damage was not shown, potentially due to limitations of these markers or low radiotherapy doses using conformal techniques. Our results also suggest subacute damage at 1 year may depend on the dose to the left ventricle. Further studies are needed, as identification of early damage could facilitate the ability to closely monitor and intervene in patients at risk for radiation-induced heart disease.

Fidaxomicin versus oral vancomycin for severe Clostridium difficile infection: a retrospective cohort study.

OBJECTIVES: This study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI). METHODS: The investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course. RESULTS: Propensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30-day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups. CONCLUSIONS: Courses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI.

Thyroid hormone receptor beta-1 expression in early breast cancer: a validation study.

PURPOSE: Preliminary data suggest that high expression of the TRß1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings. METHODS: In this prospective cohort study, we analyzed the prognostic significance of TRß1 protein expression in the breast tumors of 796 women who had undergone breast surgery in the Henrietta Banting Breast Cancer database. All women were recruited after undergoing primary surgical therapy at Women's College Hospital (Toronto, ON, Canada) between January 1987 and December 2000. Details regarding patient age at diagnosis, systemic, and local therapies, as well as pathological features of their tumor have been systematically recorded. Clinical outcomes including breast cancer recurrence and death have been updated at least once each year with a median follow-up of 9.6 years (range 0.1-21 years). RESULTS: High TRß1 expression (> 4 on the Allred score) was associated with a longer breast cancer-specific survival with a HR 0.45 (95% CI 0.33-0.61), p < 0.0001 in a univariable Cox regression model. This was maintained in a multivariable model adjusted for age, tumor size, nodal status, chemotherapy, hormone therapy, radiotherapy, surgery, and ER status with a HR of 0.61 (95% CI 0.44-0.85), p = 0.004. CONCLUSIONS: High expression of TRß1 is associated with longer breast cancer-specific survival independent of other prognostic factors. Given that low TRß expression is associated with chemotherapy resistance in-vitro, TRß1 may also serve as a predictive biomarker or even a therapeutic target given the availability of TRß agonists.

Clinical practice guidelines in breast cancer.

Background: A number of clinical practice guidelines (cpgs) concerning breast cancer (bca) screening and management are available. Here, we review the strengths and weaknesses of cpgs from various professional organizations and consensus groups with respect to their methodologic quality, recommendations, and implementability. Methods: Guidelines from four groups were reviewed with respect to two clinical scenarios: adjuvant ovarian function suppression (ofs) in premenopausal women with early-stage estrogen receptor-positive bca, and use of sentinel lymph node biopsy (slnb) after neoadjuvant chemotherapy (nac) for locally advanced bca. Guidelines from the American Society of Clinical Oncology (asco); Cancer Care Ontario's Program in Evidence Based Care (cco's pebc); the U.S. National Comprehensive Cancer Network (nccn); and the St. Gallen International Breast Cancer Consensus Conference were reviewed by two independent assessors. Guideline methodology and applicability were evaluated using the agree ii tool. Results: The quality of the cpgs was greatest for the guidelines developed by asco and cco's pebc. The nccn and St. Gallen guidelines were found to have lower scores for methodologic rigour. All guidelines scored poorly for applicability. The recommendations for ofs were similar in three guidelines. Recommendations by the various organizations for the use of slnb after nac were contradictory. Conclusions: Our review demonstrated that cpgs can be heterogeneous in methodologic quality. Low-quality cpg implementation strategies contribute to low uptake of, and adherence to, bca cpgs. Further research examining the barriers to recommendations-such as intrinsic guideline characteristics and the needs of end users-is required. The use of bca cpgs can improve the knowledge-to-practice gap and patient outcomes.

A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.

BACKGROUND: Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC). METHODS: Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 × 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel. RESULTS: Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76-1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46-0.91, P = 0.1). CONCLUSIONS: This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.

Uptake of a 21-gene expression assay in breast cancer practice: views of academic and community-based oncologists.

PURPOSE: Advances in personalized medicine have produced novel tests and treatment options for women with breast cancer. Relatively little is known about the process by which such tests are adopted into oncology practice. The objectives of the present study were to understand the experiences of medical oncologists with multigene expression profile (gep) tests, including their adoption into practice in early-stage breast cancer, and the perceptions of the oncologists about the influence of test results on treatment decision-making. METHODS: We conducted a qualitative descriptive study involving interviews with medical oncologists from academic and community cancer centres or hospitals in 8 communities in Ontario. A 21-gene breast cancer assay was used as the example of gep testing. Qualitative analytic techniques were used to identify the main themes. RESULTS: Of 28 oncologists who were approached, 21 (75%) participated in the study [median age: 43 years; 12 women (57%)]. Awareness and knowledge of gep testing were derived from several sources: international scientific meetings, participation in clinical studies, discussions with respected colleagues, and manufacturer-sponsored meetings. Oncologists observed that incorporating gep testing into their clinical practice resulted in several changes, including longer consultation times, second visits, and taking steps to minimize treatment delays. Oncologists expressed divergent opinions about the strength of evidence and added value of gep testing in guiding treatment decisions. CONCLUSIONS: Incorporation of gep testing into clinical practice in early-stage breast cancer required oncologists to make changes to their usual routines. The opinions of oncologists about the quality of evidence underpinning the test affected how much weight they gave to test results in treatment decision-making.

Advanced glycation End-products (AGEs): an emerging concern for processed food industries.

The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). The chemistry of the AGEs formation, absorption and bioavailability and their patho-biochemistry particularly in relation to different complications like diabetes and ageing discussed. The concept of AGEs receptor - RAGE is mentioned. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Different methods of detection and quantification along with types of agents used for the treatment of AGEs are reviewed. Generally, ELISA or LC-MS methods are used for analysis of foods and body fluids, however lack of universally established method highlighted. The inhibitory effect of bioactive components on AGEs by trapping variety of chemical moieties discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

(18)F-fluorodeoxyglucose positron-emission tomography-computed tomography to diagnose recurrent cancer.

BACKGROUND: Sometimes the diagnosis of recurrent cancer in patients with a previous malignancy can be challenging. This prospective cohort study assessed the clinical utility of (18)F-fluorodeoxyglucose positron-emission tomography-computed tomography ((18)F-FDG PET-CT) in the diagnosis of clinically suspected recurrence of cancer. METHODS: Patients were eligible if cancer recurrence (non-small-cell lung (NSCL), breast, head and neck, ovarian, oesophageal, Hodgkin's or non-Hodgkin's lymphoma) was suspected clinically, and if conventional imaging was non-diagnostic. Clinicians were asked to indicate their management plan before and after (18)F-FDG PET-CT scanning. The primary outcome was change in planned management after (18)F-FDG PET-CT. RESULTS: Between April 2009 and June 2011, 101 patients (age, median 65 years; 55% female) were enroled from four cancer centres in Ontario, Canada. Distribution by primary tumour type was: NSCL (55%), breast (19%), ovarian (10%), oesophageal (6%), lymphoma (6%), and head and neck (4%). Of the 99 subjects who underwent (18)F-FDG PET-CT, planned management changed after (18)F-FDG PET-CT in 52 subjects (53%, 95% confidence interval (CI), 42-63%); a major change in plan from no treatment to treatment was observed in 38 subjects (38%, 95% CI, 29-49%), and was typically associated with (18)F-FDG PET-CT findings that were positive for recurrent cancer (37 subjects). After 3 months, the stated post-(18)F-FDG PET-CT management plan was actually completed in 88 subjects (89%, 95% CI, 81-94%). CONCLUSION: In patients with suspected cancer recurrence and conventional imaging that is non-diagnostic, (18)F-FDG PET-CT often provides new information that leads to important changes in patient management.

Calibration and algorithm development for estimation of nitrogen in wheat crop using tractor mounted N-sensor.

The experiment was planned to investigate the tractor mounted N-sensor (Make Yara International) to predict nitrogen (N) for wheat crop under different nitrogen levels. It was observed that, for tractor mounted N-sensor, spectrometers can scan about 32% of total area of crop under consideration. An algorithm was developed using a linear relationship between sensor sufficiency index (SIsensor) and SISPAD to calculate the N app as a function of SISPAD. There was a strong correlation among sensor attributes (sensor value, sensor biomass, and sensor NDVI) and different N-levels. It was concluded that tillering stage is most prominent stage to predict crop yield as compared to the other stages by using sensor attributes. The algorithms developed for tillering and booting stages are useful for the prediction of N-application rates for wheat crop. N-application rates predicted by algorithm developed and sensor value were almost the same for plots with different levels of N applied.

Superior mesenteric artery syndrome: an uncommon cause of abdominal pain mimicking gastric outlet obstruction.

Upper gastrointestinal symptoms like vomiting, abdominal pain, abdominal distention may be caused by many conditions like complicated peptic/duodenal ulcer, gastritis or hiatal hernia. However, these symptoms are uncommonly produced by superior mesenteric artery (SMA) syndrome. SMA syndrome is triggered when there is narrowing of the mesenteric angle and shortening of the aortomesenteric distance. We report a case of 42-year-old female who presented with features of gastric outlet obstruction which on further investigation was revealed as SMA syndrome. The aetiology, presentation, diagnosis and management of this unusual condition are discussed.

Intramedullary chondrosarcoma of proximal humerus.

Primary chondrosarcoma is the third most frequent primary malignancy of bone after myeloma and osteosarcoma. It is ranging from slow growing nonmetastasising lesions to highly aggressive lesions. We report a case of primary intramedullary chondrosarcoma of proximal humerus. A 60-year-old female presented with pain and hard swelling involving the left arm for 5 months. Radiograph showed a lucent expansile intramedullary lesion with matrix calcification and associated soft tissue mass. CT confirmed the finding. MRI showed a lobulated lesion which is hyperintense on T2WI with low signal fibrous septae. Increased tracer uptake was seen on bone scan. Histopathology confirmed the radiology diagnosis. The patient underwent wide resection and endoprosthetic reconstruction of proximal humerus.

Cancer care Ontario guideline recommendations for hormone receptor testing in breast cancer.

Hormone receptor testing (oestrogen and progesterone) in breast cancer at the time of primary diagnosis is used to guide treatment decisions. Accurate and standardised testing methods are critical to ensure the proper classification of the patient's hormone receptor status. Recommendations were developed to improve the quality and accuracy of hormone receptor testing based on a systematic review conducted jointly by the American Society of Clinical Oncology/College of American Pathologists and Cancer Care Ontario's Program in Evidence-Based Care. Evidence-based recommendations were formulated to set standards for optimising immunohistochemistry in assessing hormone receptor status, as well as assuring quality and proficiency between and within laboratories. A formal external review was conducted to validate the relevance of these recommendations. It is anticipated that widespread adoption of these guidelines will further improve the accuracy of hormone receptor testing in Canada.

Rice bran oil an alternate bakery shortening.

Studies were carried out to replace bakery shortening with refined rice bran oil in bread preparation. Physico-chemical properties of bakery shortening and rice bran oil were studied. Rice bran oil was found to have a higher content of essential fatty acid linoleic acid (34.98%) as compared to that of bakery shortening (5.14%). Chemical composition of wheat flour used was also evaluation. Bread samples were prepared by replacing bakery shortening with rice bran oil at 0, 25, 50, 75 and 100% levels. Breads were examined for bread making quality i.e. loaf weight, loaf height, loaf volume and specific volume and organoleptic quality i.e. appearance, crust colour, crumb colour, aroma, texture, taste and overall acceptability on a 9 point hedonic scale. Statistical analysis regarding bread making quality and organoleptic quality of bread revealed that bread making and organoleptic quality of breads prepared after replacing bakery shortening with rice bran oil at 50% level varied significantly from that of control. Statistically significant variations were observed in the texture of breads prepared with shortening from that prepared after replacing bakery shortening with rice bran oil at 50% level.

Generalizability of toxicity data from oncology clinical trials to clinical practice: toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer.

BACKGROUND: The relevance of oncology trial results to clinical practice depends on whether the trial participants are similar to the actual population of patients receiving treatment for the malignancy and whether the patients are treated similarly in both circumstances. Chemotherapy treatments may be more toxic in patients of advanced age and poor performance status-patients typically excluded from clinical trials. METHODS: In a retrospective chart review that included all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy from January 2004 to September 2006 at our institution, we quantified and subsequently compared the toxicity rates of the irinotecan regimens in clinical practice with published toxicity rates from corresponding phase iii clinical trials. The primary endpoint was the incidence of grades 3 and 4 diarrhea. RESULTS: The study included 203 patients, and the irinotecan regimens considered included FOLFIRI [irinotecan, leucovorin, 5-fluorouracil (5fu)],IFL (bevacizumab, irinotecan, 5FU, leucovorin),XELIRI (capecitabine, 3-weekly irinotecan), andirinotecan monotherapy. The rates of grades 3 and 4 diarrhea for FOLFIRI, IFL, XELIRI, and irinotecan monotherapy in clinical practice were 10%, 15%, 17%, and 21% as compared with 10%, 23%, 20%, and 31% respectively in clinical trials. When only patients meeting trial performance status and age criteria were analyzed, the rates of grades 3 and 4 diarrhea by regimen were 11%, 20%, 19%, and 26% respectively. CONCLUSIONS: Overall, the toxicity rates for FOLFIRI and irinotecan monotherapy in non-trial patients were not statistically different from the rates quoted in published clinical trials.

Some quality aspects of fish patties prepared from an Indian major carp, Labeo rohita (Ham.).

Six different types of fish patties were prepared from de-boned meat of three weight groups (250 500 g, 501-750 g, and 751-1,000 g) of an Indian major carp, Labeo rohita, using two extenders (boiled potato and corn flour). The weight of the fish and the type of the extender affected the nutritional quality of the patties. Cooking lowered the crude protein but increased the total lipid, total soluble sugars, and contents of the patties. Cooking yield increased with an increase in the weight of the fish. Similarly, the use of corn flour as the extender resulted in a higher cooking yield and higher fat retention capacity than boiled potato. The type of extender had no effect on the water-holding capacity of the patties. The weight of the fish and the extender had no significant effect on appearance, colour, flavour, taste, and the overall acceptability of the product. However, the patties prepared from 250-500 g and 501-750 g weight groups with corn flour as the extender had a significantly higher score for their texture. The total plate count suggested that the patties were safe (from microbiological point of view) up to a storage period of 80 days.

Differential induction of pyruvate decarboxylase subunits and transcripts in anoxic rice seedlings.

In 2-d-old rice (Oryza sativa L.) seedlings subjected to anoxic stress, pyruvate decarboxylase (PDC) activity increased 9-fold during a 168-h period. A polyclonal PDC antiserum that recognized alpha- and beta-subunits was used to quantify PDC protein by an enzyme-linked immunosorbant assay and showed a 5.6-fold increase, suggesting that the anoxically induced enzyme has a higher specific activity than the PDC isoform present under normoxia. Immunoblot analysis showed that levels of both PDC subunits were induced by anoxia. Immunoprecipitation of proteins labeled in vivo during anoxic treatment demonstrated that the alpha-subunit was preferentially synthesized at the onset of anoxia. Two partial cDNAs, including a novel sequence, were cloned from a cDNA library made from seedlings subjected to anoxia for 6 h. Gene-specific probes used to quantify northern blots showed that two or three PDC mRNAs are differentially induced by anoxia in rice seedlings. Immunoprecipitation of in vitro translation products of mRNAs isolated a different times of anoxic treatment confirmed this findings Our results suggest that anoxic induction of rice PDC involves transcriptional and posttranscriptional regulation of gene expression as well as differences in enzyme characteristics.

Vitamin B6 deficiency and galactose induced alterations in morphology and osmotic fragility of rat erythrocytes.

Recently, red blood cells have been investigated mainly for alterations in ion transporting capacity, membrane bound enzymes or modifications in the structure of its individual constituents in clinical and experimental urolithiasis. However, the implication of such modifications on the physical state or morphology of cells has not been investigated. Scanning electron microscopic studies performed in vitamin B6 deficient and/or galactose fed rat (established hyperoxaluric models) erythrocytes, showed the presence of large number of stomatocytes, spherocytes and other variously deformed cells as compared to discocytic cells seen in normal control group. These changes in shape were in concurrence with red cell osmotic fragility, which decreased both in vitamin B6 deficient and vitamin B6 deficient + galactose fed group (19 % and 33 % hemolysis at 4 g/l NaCl, respectively) while it increased in galactose control group (73 % hemolysis at 4 g/l NaCl) as compared to normal control group (55 % hemolysis at 4 g/l NaCl). These morphological and physical state alterations could be correlated with red blood cells' membrane cholesterol and phospholipid sub-class distribution. These findings suggest that some structural membrane changes occur due to vitamin B6 deficiency and/or galactose feeding, which may be responsible for the altered membrane functions known to be associated with pathogenesis of urolithiasis.