The Impact of Preoperative Breast MRI on Timing of Surgical Management in Newly Diagnosed Breast Cancer.

Purpose: Preoperative breast MRI has been recommended at our center since 2016 for invasive lobular carcinoma and cancers in dense breasts. This study examined how preoperative breast MRI impacted surgical timing and outcomes for patients with newly diagnosed breast cancer. Methods: Retrospective single-center study of consecutive women diagnosed with new breast cancer between June 1, 2019, and March 1, 2021, in whom preoperative breast MRI was recommended. MRI, tumor histology, breast density, post-MRI biopsy, positive predictive value of biopsy (PPV3), surgery, and margin status were recorded. Time from diagnosis to surgery was compared using t-tests. Results: There were 1054 patients reviewed, and 356 were included (mean age 60.9). Of these, 44.4% (158/356) underwent preoperative breast MRI, and 55.6% (198/356) did not. MRI referral was more likely for invasive lobular carcinoma, multifocal disease, and younger patients. Following preoperative MRI, 29.1% (46/158) patients required additional breast biopsies before surgery, for a PPV3 of 37% (17/46). The time between biopsy and surgery was 55.8 ± 21.4 days for patients with the MRI, compared to 42.8 ± 20.3 days for those without (P < .00001). MRI was not associated with the type of surgery (mastectomy vs breastconserving surgery) (P = .44) or rate of positive surgical margins (P = .52). Conclusion: Among patients who underwent preoperative breast MRI, we observed significant delays to surgery by almost 2 weeks. When preoperative MRI is requested, efforts should be made to mitigate associated delays.

Adverse Events Associated with Intra-Arterial Administration of Gadolinium-Based Contrast Agents: A Systematic Review and Meta-Analysis.

PURPOSE: To determine the risk of immediate hypersensitivity reactions (HRs), contrast-associated acute kidney injury (CA-AKI), nephrogenic systemic fibrosis (NSF), and gadolinium retention associated with use of intra-arterial gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from 1988 (GBCAs approved for clinical use) to March 2021 for studies reporting adverse events associated with intra-arterial administration of GBCAs. The number of adverse events and GBCA administrations were used to calculate incidence in individual studies, and results across studies were pooled using random-effects meta-analysis. RESULTS: There were 72 studies (patients = 1,221) that reported on HR, 59 studies (patients = 1,142) that reported on CA-AKI, and 6 studies (patients = 291) that reported on NSF. No studies reported gadolinium retention as an outcome. Based on 5 events and 1,451 GBCA administrations, the incidence of HR per 100 administrations was 0.95 (95% CI, 0.52-1.51). Based on 90 events and 1,318 GBCA administrations, the incidence of CA-AKI per 100 administrations was 5.94 (95% CI, 3.92-8.34). Based on 7 events and 361 GBCA administrations, the incidence of NSF per 100 Group I GBCA administrations was 4.72 (95% CI, 0.35-13.70). There were no unconfounded NSF events after Group II GBCA administration. CONCLUSIONS: HRs to intra-arterial administration of GBCAs are rare, with no serious reactions. Limited data demonstrate a higher-than-expected rate of CA-AKI; however, multiple confounding factors were noted. Thus, any causative link of CA-AKI to GBCA remains controversial. Also, severe physiologic reactions (including life-threatening arrhythmias) during coronary angiography have been reported.

Association of Accuracy, Conclusions, and Reporting Completeness With Acceptance by Radiology Conferences and Journals.

BACKGROUND: Preferential publication of studies with positive findings can lead to overestimation of diagnostic test accuracy (i.e. publication bias). Understanding the contribution of the editorial process to publication bias could inform interventions to optimize the evidence guiding clinical decisions. PURPOSE/HYPOTHESIS: To evaluate whether accuracy estimates, abstract conclusion positivity, and completeness of abstract reporting are associated with acceptance to radiology conferences and journals. STUDY TYPE: Meta-research. POPULATION: Abstracts submitted to radiology conferences (European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and International Society for Magnetic Resonance in Medicine (ISMRM)) from 2008 to 2018 and manuscripts submitted to radiology journals (Radiology, Journal of Magnetic Resonance Imaging [JMRI]) from 2017 to 2018. Primary clinical studies evaluating sensitivity and specificity of a diagnostic imaging test in humans with available editorial decisions were included. ASSESSMENT: Primary variables (Youden's index [YI > 0.8 vs. <0.8], abstract conclusion positivity [positive vs. neutral/negative], number of reported items on the Standards for Reporting of Diagnostic Accuracy Studies [STARD] for Abstract guideline) and confounding variables (prospective vs. retrospective/unreported, sample size, study duration, interobserver agreement assessment, subspecialty, modality) were extracted. STATISTICAL TESTS: Multivariable logistic regression to obtain adjusted odds ratio (OR) as a measure of the association between the primary variables and acceptance by radiology conferences and journals; 95% confidence intervals (CIs) and P-values were obtained; the threshold for statistical significance was P < 0.05. RESULTS: A total of 1000 conference abstracts (500 ESGAR and 500 ISMRM) and 1000 journal manuscripts (505 Radiology and 495 JMRI) were included. Conference abstract acceptance was not significantly associated with YI (adjusted OR = 0.97 for YI > 0.8; CI = 0.70-1.35), conclusion positivity (OR = 1.21 for positive conclusions; CI = 0.75-1.90) or STARD for Abstracts adherence (OR = 0.96 per unit increase in reported items; CI = 0.82-1.18). Manuscripts with positive abstract conclusions were less likely to be accepted by radiology journals (OR = 0.45; CI = 0.24-0.86), while YI (OR = 0.85; CI = 0.56-1.29) and STARD for Abstracts adherence (OR = 1.06; CI = 0.87-1.30) showed no significant association. Positive conclusions were present in 86.7% of submitted conference abstracts and 90.2% of journal manuscripts. DATA CONCLUSION: Diagnostic test accuracy studies with positive findings were not preferentially accepted by the evaluated radiology conferences or journals. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Risk of nephrogenic systemic fibrosis (NSF) in oncology patients receiving gadoxetic acid and updated risk of estimate of NSF in patients receiving gadoxetic acid with moderate and severe renal impairment.

OBJECTIVES: Gadoxetic acid (GA) is a half-biliary excreted gadolinium-based contrast agent (GBCA) administered at lower dose than gadobenic acid with similar ionic structure. Gadobenic acid is considered low-risk for nephrogenic systemic fibrosis (NSF) in patients with impaired renal function; however, safety of GA is unclear. The objective of this study was to determine the incidence of NSF in oncology patients undergoing GA-enhanced MRI and to update the risk estimate of NSF in patients receiving GA with severe renal impairment. MATERIALS AND METHODS: We retrospectively identified GA-enhanced MRI performed for treatment planning in confirmed cancer patients between March 2011 and December 2020. Serum creatinine values within 180 days of GA administration were retrieved and estimated glomerular filtration rate (eGFR) calculated. The eGFR value nearest to each MRI examination was used. The search result was linked to a prospectively maintained registry of reported cases of NSF. An updated literature review was conducted to identify published cases of NSF related to GA administration in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2 or on dialysis) and the incidence of NSF with 95% confidence intervals (CI) was determined combining published data with our results. RESULTS: 192 oncology patients underwent GA-enhanced MRI, mean age was 65.6 ± 11.8 years with 73 women. The mean eGFR was 89.6 ± 33.0 mL/min/1.73 m2. There were 33 patients with moderate (eGFR 30-60 mL/min/1.73 m2) and 1 patient with severe (eGFR < 30 mL/min/1.73 m2) renal impairment. There were no reported cases of NSF. Updated literature review including our results identified 340 patients with severe renal impairment or on dialysis with zero cases of NSF (0/340; 95% confidence intervals 0% and 0.9%). CONCLUSION: No cases of NSF were documented in this study related to gadoxetic acid use in oncology patients, including those with moderate and severe renal impairment. Recent data indicate use of gadoxetic acid in patients with renal impairment can be considered low-risk.

Black students applying and admitted to medicine in the province of Quebec, Canada: what do we know so far?

To address the underrepresentation of Black students in medical schools in Canada and identify barriers in selection processes, we compare data from the latest Canadian census to that of an exit-survey conducted after a situational judgment test (Casper) among medical school applicants and from questionnaires done after selection interviews in Quebec, Canada. The proportion of Black people aged 15-34 years old in Quebec in 2016 was 5.3% province-wide and 8.2% in the Montreal metropolitan area. The proportion in the applicant pool for 2020 in Quebec was estimated to be 4.5% based on Casper exit-survey data. Comparatively, it is estimated that Black people represented 1.8% of applicants invited to admission interviews and 1.2% of admitted students in Quebec in 2019. Although data from different cohorts and data sources do not allow for direct comparisons, these numbers suggest that Black students applying to medical school are disproportionately rejected at the first step compared to non-Black students. Longitudinal data collection among medical school applicants will be necessary to monitor the situation. Further studies are required to pinpoint the factors contributing to this underrepresentation, to keep improving the equity of our selection processes.

Afin de remédier à la sous-représentation des étudiants noirs dans les facultés de médecine au Canada et de cibler les obstacles qu'ils rencontrent dans le processus de sélection, nous comparons les données du dernier recensement canadien avec celles d'un sondage réalisé à la suite d'un test de jugement situationnel (Casper) auprès de candidats ayant fait une demande d'admission dans un programme de doctorat en médecine et celles d'un sondage réalisé à la suite d'entretiens de sélection au Québec (Canada). La proportion de personnes noires âgées de 15 à 34 ans au Québec en 2016 était de 5,3 % à l'échelle de la province et de 8,2 % dans la région métropolitaine de Montréal. La proportion de cette population dans le bassin de candidats pour 2020 au Québec a été estimée à 4,5 % sur la base des données du sondage Casper. À titre de comparaison, on estime que les Noirs représentaient 1,8 % des candidats invités aux entrevues d'admission et 1,2 % des étudiants admis au Québec en 2019. Bien que les données pour les différentes cohortes, provenant de surcroît de sources différentes, ne permettent pas d'établir des comparaisons directes, ces chiffres suggèrent que les étudiants noirs qui demandent à être admis en médecine sont rejetés de manière disproportionnée à la première étape par rapport aux étudiants non noirs. Une collecte de données longitudinales parmi les candidats sera nécessaire pour suivre l'évolution de la situation, ainsi que d'autres études pour découvrir les facteurs qui contribuent à cette sous-représentation, notamment dans une visée d'amélioration de l'équité dans les processus de sélection.

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226.

This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design. Both weight-based and fixed dosing of Du and Tr were explored. Du was continued until progression. Tr dosing was finite (up to 6 doses) with increasing dose and/or frequency by DL. 136 patients were enrolled. The majority of drug-related adverse events (AEs) were ≤ grade 2 and attributable to chemotherapy. AEs considered related to immunotherapy were mainly ≤ grade 2; the most frequent (occurring ≥10 %) were colitis/diarrhea, skin, and thyroid dysfunction. Seven patients had DLTs including pneumonitis, myocarditis, diarrhea, encephalitis, motor neuropathy, and enterocolitis. There were 2 treatment-related deaths. Tr and Du exposures did not appear affected by chemotherapy. Among the 73 non-small cell lung cancer (NSCLC) patients treated, the objective response rate was 51 % (95 %CI = 38.7-62.6 %) with a median progression-free and overall survival of 6.5 months (95 % CI = 5.5-9.4 months) and 19.8 months (95 % CI = 14.8 months - not yet reached) respectively. Anti-tumour activity was observed across PD-L1 subtypes. Du 1500 mg q3w and Tr 75 mg q3wx5 can be safely combined with platinum-doublet chemotherapy. Efficacy among NSCLC patients appears comparable to results from other immunotherapy and chemotherapy combination trials. NCT02537418.

Multi-detector CT for suspected hip fragility fractures: A diagnostic test accuracy systematic review and meta-analysis.

To perform a systematic review (SR) and meta-analysis to determine the diagnostic test accuracy (DTA) of Multi-Detector Computed Tomography (MDCT) for detecting proximal femoral (hip) fragility fractures in patients with a negative initial radiograph. MEDLINE and EMBASE were searched to identify relevant studies published between January 2000 and May 2018. Articles underwent title and abstract screening followed by full-text screening. Study inclusion criteria are patients with suspected hip fracture, negative initial radiograph, MDCT as the index test, magnetic resonance imaging (MRI) or clinical follow-up as the reference standard, and DTA measure as the outcome. Demographic, methodologic, and study outcome data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. DTA metrics were pooled using bivariate random-effects meta-analysis. From an initial 1385 studies, four studies reporting on 418 patients (174 with hip fractures) were included. Pooled summary statistics included the following: sensitivity (87%; 95% confidence interval [CI] 79-93), specificity (98%; 95% CI 95-99), and the area under the summary receiver operating characteristic (ROC) curve (0.972). MDCT has a high specificity for detecting hip fragility fractures, comparable to MRI, but a lower sensitivity. Local institutional factors may play a role in whether a patient receives MDCT or MRI, as imaging should not be delayed. If there is ongoing concern for fracture in a patient with a negative MDCT, MRI should be performed. Cautious interpretation of the results is warranted given the risk of bias and small sample size.

Citation bias in imaging research: are studies with higher diagnostic accuracy estimates cited more often?

OBJECTIVES: To assess the risk of citation bias in imaging diagnostic accuracy research by evaluating whether studies with higher accuracy estimates are cited more frequently than those with lower accuracy estimates. METHODS: We searched Medline for diagnostic accuracy meta-analyses published in imaging journals from January 2005 to April 2016. Primary studies from the meta-analyses were screened; those assessing the diagnostic accuracy of an imaging test and reporting sensitivity and specificity were eligible for inclusion. Studies not indexed in Web of Science, duplicates, and inaccessible articles were excluded. Topic (modality/subspecialty), study design, sample size, journal impact factor, publication date, times cited, sensitivity, and specificity were extracted for each study. Negative binomial regression was performed to evaluate the association of citation rate (times cited per month since publication) with Youden's index (sensitivity + specificity -1), highest sensitivity, and highest specificity, controlling for the potential confounding effects of modality, subspecialty, impact factor, study design, sample size, and source meta-analysis. RESULTS: There were 1016 primary studies included. A positive association between Youden's index and citation rate was present, with a regression coefficient of 0.33 (p = 0.016). The regression coefficient for sensitivity was 0.41 (p = 0.034), and for specificity, 0.32 (p = 0.15). CONCLUSION: A positive association exists between diagnostic accuracy estimates and citation rates, indicating that there is evidence of citation bias in imaging diagnostic accuracy literature. Overestimation of imaging test accuracy may contribute to patient harm from incorrect interpretation of test results. KEY POINTS: • Studies with higher accuracy estimates may be cited more frequently than those with lower accuracy estimates. • This citation bias could lead clinicians, reviews, and clinical practice guidelines to overestimate the accuracy of imaging tests, contributing to patient harm from incorrect interpretation of test results.

Water-Related Vaginal Injury: A Case Report and Review of the Literature.

BACKGROUND: Vaginal injury can result from entry of water into the vagina under high pressure. Previously reported cases describe water-jet vaginal injuries in women participating in water-related activities, including: water skiing, personal watercraft use, waterslides, water hose and fountains, with and without foreign body in situ. CASE: We describe the case of a severe vaginal laceration and hemorrhage in a 44-year-old female from a high-pressure water-jet generated during a water-ski fall requiring operative repair. Timely management resulted in excellent patient outcome. CONCLUSION: A literature review demonstrated that, although uncommon, watersport-related gynaecologic injuries can be life-threatening, and women who regularly engage in watersports can be counselled regarding potential preventative measures. Physicians encountering patients with these injuries should rule out intraperitoneal injury and consider benefits of antibiotics.

Chronic mild stress exacerbates severity of experimental autoimmune encephalomyelitis in association with altered non-coding RNA and metabolic biomarkers.

The causal factors determining the onset and severity of multiple sclerosis (MS) are not well understood. Here, we investigated the influence of chronic stress on clinical symptoms, metabolic and epigenetic manifestations of experimental autoimmune encephalomyelitis (EAE), a common animal model of MS. Lewis rats were immunized for monophasic EAE with MBP69-88 and were exposed to chronic stress for 37days starting 7days prior to immunization. The exposure to stress accelerated and exacerbated the clinical symptoms of EAE. Both stress and EAE also disrupted metabolic status as indicated by trace elemental analysis in body hair. Stress particularly exacerbated chlorine deposition in EAE animals. Moreover, deep sequencing revealed a considerable impact of stress on microRNA expression in EAE. EAE by itself upregulated microRNA expression in lumbar spinal cord, including miR-21, miR-142-3p, miR-142-5p, miR-146a, and miR-155. Stress in EAE further up-regulated miR-16, miR-146a and miR-155 levels. The latter two microRNAs are recognized biomarkers of human MS. Thus, stress may synergistically exacerbate severity of EAE by altering epigenetic regulatory pathways. The findings suggest that stress may represent a significant risk factor for symptomatic deterioration in MS. Stress-related metabolic and microRNA signatures support their value as biomarkers for predicting the risk and severity of MS.

Outcomes of intensity-modulated radiotherapy versus conventional radiotherapy for hypopharyngeal cancer.

BACKGROUND: The purpose of this study was to discuss if the adoption of intensity-modulated radiotherapy (IMRT) for hypopharyngeal squamous cell carcinoma (SCC) has improved the outcome. METHODS: We compared 3-dimensional (3D) radiotherapy (RT) and IMRT in all patients with hypopharyngeal SCC treated with curative intent RT or chemoradiation therapy (CRT) from January 1, 2000, to February 28, 2010. Locoregional control, overall survival (OS), distant relapse rate, larynx preservation rate, and enteral feeding tube duration were analyzed. RESULTS: Of 181 consecutive patients, 90 received 3D-RT and 91 received IMRT. At 3 years, the IMRT group had higher locoregional control compared with the 3D-RT group (75% vs 58%; p = .003), but similar OS (50% vs 52%; p = .99), distant relapse rate (23% vs 20%; p = .79), and larynx-preservation rate (90% vs 86%; p = .16). The 2-year enteral feeding tube dependency rate was similar in both groups (19% vs 18%; p = .12). CONCLUSION: Patients with hypopharyngeal SCC treated with IMRT showed a higher locoregional control compared with 3D-RT. However, distant-relapse rate and OS remain comparable between treatment techniques.

We can predict postpalatoplasty velopharyngeal insufficiency in cleft palate patients.

OBJECTIVES/HYPOTHESIS: To find an anatomical measurement of the cleft palate (or a calculated parameter) that predicts the occurrence of velopharyngeal insufficiency (VPI) after palatal cleft repair. STUDY DESIGN: Retrospective cohort study. METHODS: Charts were reviewed from cleft palate patients who underwent palatoplasty by the Von Langenbeck technique for isolated cleft palate or Bardach two-flap palatoplasty for cleft lip-palate. Seven anatomical cleft parameters were prospectively measured during the palatoplasty procedure. Three blinded speech-language pathologists retrospectively scored the clinically assessed VPI at 4 years of age. The recommendation of pharyngoplasty was also used as an indicator of VPI. RESULTS: From 1993 to 2008, 67 patients were enrolled in the study. The best predicting parameter was the ratio a/(30 - b1), in which a is defined as the posterior gap between the soft palate and the posterior pharyngeal wall and b1 is the width of the cleft at the hard palate level. An a/(30 - b1) ratio >0.7 to 0.8 is associated with a higher risk of developing VPI (relative risk = 2.2-5.1, sensitivity = 72%-81%, P < .03). CONCLUSIONS: The width of the cleft at the hard palate level and the posterior gap between the soft palate and the posterior pharyngeal wall were found to be the most significant parameters in predicting VPI. The best correlation was obtained with the ratio a/(30 - b1). LEVEL OF EVIDENCE: 4.

Isolated versus pierre robin sequence cleft palates: are they different?

OBJECTIVE: To determine if there are any differences in size between isolated cleft palates (CPs) and those associated with Pierre Robin (PR) sequence. STUDY DESIGN: Prospective case series. SETTINGS: Tertiary care hospital. SUBJECTS AND METHODS: From 1993 to 2011, nonsyndromic isolated CP and PR sequence cases were classified as severe if the patients had respiratory or feeding difficulties. While patients were under general anesthesia, seven anatomical cleft parameters were prospectively measured in the operating room at the time of palatoplasty. RESULTS: Fifty-seven patients without the PR sequence and 36 patients with the PR sequence were enrolled. Within the PR group, 61% of cases were mild and 39% were severe. A larger soft palate width was found to be statistically significant in a comparison of the severe PR cases with the isolated clefts (P < .005) and mild PR (P < .05), respectively. For the hard palate width, a statistically significant difference was found in a comparison of the narrower isolated cleft cases with the mild PR (P < .05) and the severe PR cases (P < .05), respectively. A shorter cleft length was found to be statistically significant in isolated clefts versus both the clefts of the mild PR (P < .05) and the severe PR cases (P < .05). CONCLUSIONS: The patients with PR sequence presented statistically significant different cleft characteristics. The increased width of the cleft at the soft palate level showed the greatest correlation with increased airway and feeding problems.

A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer.

AIM: This phase I/II study of saracatinib in combination with gemcitabine in patients with advanced pancreatic cancer was conducted by the NCIC Clinical Trials Group. The aims were to define the recommended phase II dose (RP2D) of saracatinib when combined with gemcitabine, and assess the efficacy of this combination in advanced pancreatic cancer. PATIENTS AND METHODS: Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m(2)) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥ 4 months (SD4) rate; if ≥ 8 patients had OR+SD4, the study would proceed to stage 2. RESULTS: Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients. CONCLUSION: Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone.

Can we predict a difficult intubation in cleft lip/palate patients?

OBJECTIVE: To find predictors of a difficult intubation in infants with an isolated or a syndromic cleft lip/palate. STUDY DESIGN: Retrospective review: single-blind trial. SETTINGS: Tertiary care centre. METHODS: A total of 145 infants born with cleft lip/palate were enrolled. Three clinical and seven lip/palate anatomic parameters were evaluated. The grade of intubation was determined by the anesthesiologist at the time of the labioplasty/staphylorrhaphy surgery at 3 and 10 months, respectively. MAIN OUTCOME MEASURE: Intubation grade. RESULTS: The relative risk of a difficult intubation in the cleft lip, cleft palate without the Pierre Robin sequence, cleft lip-palate, and cleft palate with Pierre Robin sequence groups was 0, 2.7, 10, and 23%, respectively. The infants born with the Pierre Robin sequence had a statistically significant higher intubation grade. The degree of difficulty was increased in cases with early airway and feeding problems (p < .0001). Within the group of cleft palate patients without any lip malformation, a wider cleft was associated with a higher intubation grade with statistical significance (p  =  .0323). CONCLUSIONS: Infants born with Pierre Robin sequence have a statistically significantly higher risk of difficult intubation. Within this group, of all the studied factors, a clinical history of early airway and feeding problems was the best predictor of a difficult endotracheal intubation. In cleft palate patients without any cleft lip, larger width of the cleft is also a significant predictor.

Complete frozen section margins for cancer of the tongue: part 1: animal experience.

OBJECTIVE: Positive margins for squamous cell carcinoma of the oral tongue on final pathology are a poor prognostic factor associated with a higher likelihood of local recurrence. Obtaining margin status in a relatively short time by using complete frozen sections, such as Mohs margins for skin cancer, would lower the recurrence rate. The goal of this study was to compare, on pig tongue, the efficacy of different techniques used to obtain complete frozen sections on histologic glass slides of optimal quality. STUDY DESIGN: We compared the quality of frozen section glass slides on fresh pig tongues. The partial glossectomy was executed with either a sharp instrument (scalpel and scissors), electrocautery in the cutting mode, or electrocautery at the coagulation mode. For each of the three methods, we also compared the frozen section, obtained on the line of resection and for a thickness of 1 to 1.3 mm, using either the cryostat or isopentane for the freezing phase. The percentage and quality of epithelium and muscle present on histologic glass slides were assessed by a pathologist independently. RESULTS: Complete frozen margins of high quality were obtained in a relatively short time for all techniques (28-38 minutes). Sharp dissection showed better results: a shorter processing time for the specimens and better quality for the histologic glass slides. Using cryostat or isopentane for the freezing phase did not show any significant difference. CONCLUSION AND SIGNIFICANCE: Complete frozen margins (Mohs margins) of high quality are feasible. Histologic glass slides of very good quality are obtained when using a sharp dissection technique. For the freezing period, both isopentane and cryostat offer very good results. This approach is appropriate on animals and needs further study in clinical situations. The human experience will be presented in the next article which is: Complete frozen section margins (with measurable 1 or 5 mm thick free margin) for cancer of the oral tongue (Clinical experience Part 2 [CSO2008]).

Complete frozen section margins (with measurable 1 or 5 mm thick free margin) for cancer of the tongue: part 2: clinical experience.

OBJECTIVE: To obtain completely negative margins of 1 to 5 mm at the time of surgery for oral tongue squamous cell carcinoma by using a Mohs-like technique. STUDY DESIGN: Case series of 12 patients (4 T1, 5 T2, 2 T3, 1 T4) and a review of the literature. RESULTS: For the first six cases, complete, colored for precise orientation, frozen margins of high quality were obtained in a relatively short time (20-75 minutes). Four levels were evaluated within 1 to 2 mm of the line of resection. Obtaining complete free margins for a thickness of 5 mm was done for the last six cases. The time was longer (70-120 minutes) but did not exceed the time necessary to perform the neck dissection, except for one patient. The technique using the scalpel and scissors implied slightly more bleeding, which was never a problem. We have observed no recurrence for these 12 patients (follow-up 12-34 months). CONCLUSION: The review of the literature demonstrates that invaded and close margins confer a higher recurrence rate. We have obtained 1 to 2 mm (first six patients) and 5 mm (last six patients) thick, complete, oriented, and free frozen margins with success and no recurrence, but the follow-up was short. We prefer to obtain a 5 mm thick margin when possible. The delay to obtain the pathologic result is reasonable. This approach should reduce dramatically the problem of positive and close margins at the final pathology and, consequently, the rate of local control.

Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study.

PURPOSE This phase II/III double-blind study assessed efficacy and safety of cediranib with standard chemotherapy as initial therapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Paclitaxel (200 mg/m(2)) and carboplatin (area under the serum concentration-time curve 6) were given every 3 weeks, with daily oral cediranib or placebo at 30 mg (first 45 patients received 45 mg). Progression-free survival (PFS) was the primary outcome of the phase II interim analysis; phase III would proceed if the hazard ratio (HR) for PFS < or = 0.77 and toxicity were acceptable. Results A total of 296 patients were enrolled, 251 to the 30-mg cohort. The phase II interim analysis demonstrated a significantly higher response rate (RR) for cediranib than for placebo, HR of 0.77 for PFS, no excess hemoptysis, and a similar number of deaths in each arm. The study was halted to review imbalances in assigned causes of death. In the primary phase II analysis (30-mg cohort), the adjusted HR for PFS was 0.77 (95% CI, 0.56 to 1.08) with a higher RR for cediranib than for placebo (38% v 16%; P < .0001). Cediranib patients had more hypertension, hypothyroidism, hand-foot syndrome, and GI toxicity. Hypoalbuminemia, age > or = 65 years, and female sex predicted increased toxicity. Survival update (N = 296) 10 months after study unblinding favored cediranib over placebo (median of 10.5 months v 10.1 months; HR, 0.78; 95% CI, 0.57 to 1.06; P = .11). Causes of death in the cediranib 30-mg cohort were NSCLC (81%), protocol toxicity +/- NSCLC (13%), and other (6%); for the placebo group, they were 98%, 0%, and 2%, respectively. CONCLUSION The addition of cediranib to carboplatin/paclitaxel results in improved response and PFS, but does not appear tolerable at a 30-mg dose. Consequently, the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a randomized, double-blind, placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC.

Phase I study of cediranib in combination with oxaliplatin and infusional 5-Fluorouracil in patients with advanced colorectal cancer.

PURPOSE: Cediranib is a potent oral inhibitor of the tyrosine kinase activity associated with all subtypes of vascular endothelial growth factor receptor. Purposes of this study were to determine the recommended phase II dose of cediranib in combination with standard doses of modified FOLFOX-6 (mFOLFOX-6), and the tolerability, safety, pharmacokinetics, and antitumor activity of this combination in patients with untreated metastatic colorectal cancer. EXPERIMENTAL DESIGN: Cediranib was administered daily orally at a starting dose of 30 mg and escalated to 45 mg daily, and mFOLFOX-6 was repeated every 14 days. Pharmacokinetic studies were done for oxaliplatin, 5-fluorouracil, and cediranib. Response was assessed by Response Evaluation Criteria in Solid Tumors every four cycles. RESULTS: Sixteen patients received 150 cycles of treatment (median, 6; range, 1-20 cycles). Of 9 patients enrolled at the 30-mg dose level, 1 patient experienced grade 3 diarrhea during cycle 1. No dose-limiting toxicity was observed in 7 patients at the 45-mg dose level. Common grade 3 toxicities related to cediranib included hypertension, diarrhea, fatigue, and anorexia. Of 14 patients evaluable for response, there were 6 partial responses (42.9%; 95% confidence interval, 17.7-71.1%) and 6 stable disease. The median progression-free survival was 9.3 months. There were no pharmacokinetic interactions between cediranib and 5-fluorouracil or free plasma intact oxaliplatin. CONCLUSIONS: Toxicities of this combination were manageable and consistent with previous studies. The recommended phase II dose is cediranib at 30 mg daily continuously in combination with standard doses of mFOLFOX-6. Cediranib and mFOLFOX-6 has promising antitumor activity and this combination warrants further investigation.

Dosimetric impact and theoretical clinical benefits of fiducial markers for dose escalated prostate cancer radiation treatment.

PURPOSE: To assess the impact of fiducial markers and daily kilovoltage imaging (FM-kV) on dose-volume histogram (DVH) parameters and normal tissue complication probabilities (NTCPs) for the rectum and bladder during prostate cancer radiotherapy. METHODS AND MATERIALS: Two different setup scenarios were compared for 20 patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer to a total dose of 76 Gy: a traditional setup with planning target volume (PTV) margins associated with skin mark alignment vs. another setup using FM-kV. Various DVH parameters were compared, including Radiation Therapy Oncology Group (RTOG) dose-volume constraints for the rectum and bladder. Analysis of NTCPs was also performed according to the Lyman model. RESULTS: With the traditional setup, 85% of patients had rectal V70(Gy) >25% compared with 45% with FM-kV. Moreover, 30% of patients with traditional setup vs. 5% with FM-kV did not fulfill at least 3 RTOG constraint parameters for the rectum. Mean rectal and bladder dose were 4.7 Gy and 6.7 Gy less, respectively, with FM-kV. The NTCP for the rectum was 11.5% with the traditional setup and 9% with FM-kV. This indicates that with FM-kV, the prescription dose could be increased by 2.1 Gy while keeping the same level of late rectal toxicity as with the traditional setup. CONCLUSIONS: Use of FM-kV is an efficient way of lowering the proportion of patients not fulfilling RTOG rectal and bladder dose-volume constraints. The results of the NTCP analysis suggest that the PTV margin reduction allowed by FM-kV should decrease the rate of late rectal toxicities or may allow moderate dose escalation.