Secular trends in the survival of patients with laryngeal carcinoma, 1995-2007.

BACKGROUND: Recent reports suggest a decline over time in the survival of patients newly diagnosed with laryngeal cancer in spite of developments in treatment practices. Our study set out to determine whether the survival of patients with laryngeal cancer in Ontario has changed over time. METHODS: This population-based cohort study of patients diagnosed with laryngeal cancer in the province of Ontario between 1995 and 2007 used data extracted from linked provincial administrative and registry databases. Its main outcomes were overall survival, laryngectomy-free survival, and survival ratio relative to an age- and sex-matched general population. RESULTS: The 4298 patients newly diagnosed with laryngeal cancer during the period of interest were predominantly men (n = 3615, 84.1%) with glottic cancer (n = 2787, 64.8%); mean age in the group was 66 years (interquartile range: 59-74 years). Patient demographics did not significantly change over time. Overall, 5-year survival was 57.4%; laryngectomy-free survival was 45.4%. Comparing patients from three eras (1995-1998, 1999-2003, 2004-2007) and adjusting for age, sex, and comorbidity status, we observed no differences in overall survival or laryngectomy-free survival over time. The 5-year relative survival ratio for patients with laryngeal cancer compared with an age- and sex-matched group from the general population was 81.1% for glottic cancer and 44.5% for supraglottic cancer. CONCLUSIONS: In patients with a new diagnosis of laryngeal cancer, overall and laryngectomy-free survival have remained unchanged since the mid-1990s. New methods to improve survival and the rate of laryngeal preservation in this patient population are needed.

Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay.

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting. Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time between appointments. Clinical and demographic data were collected for all patients. Results: The average time for patients to have their first appointment at the mdt clinic was 15.1 months, consisting of 3.9 months for patients to see a health care provider (hcp) for the first time since symptom onset and 10.7 months from first hcp appointment to the mdt clinic. Patients saw an average of 3 hcps before the mdt clinic visit (range: 1-7). No significant differences in time to presentation were found based on stage at presentation or anatomic site. Conclusions: At our tertiary care cancer centre, a patient's clinical pathway to being seen at the mdt clinic shows significant delays, particularly in the time from the first hcp visit to mdt referral. Possible methods to mitigate delay include education about hnc for patients and providers alike, and a more streamlined referral system.

Survival of patients with subglottic squamous cell carcinoma.

Objective: Subglottic squamous cell carcinoma is a rare subsite of laryngeal cancer that behaves more aggressively and portends a worse prognosis. Using a population-based cancer registry, our objective was to report overall survival (os) and laryngectomy-free survival (lfs) in patients diagnosed with subglottic squamous cell carcinoma, and to determine whether primary laryngectomy results in improved survival. Methods: This retrospective population-based study considered patients with a new diagnosis of squamous cell carcinoma in the province of Ontario over a 15-year period (1995-2009). The Ontario Cancer Registry was examined for patients with the diagnosis of interest during the period of interest. Linked population-based databases were used to obtain patient demographics, comorbidity measures, staging, survival, and primary treatment with laryngectomy. Results: Of 4927 patients identified to have laryngeal carcinoma, 89 were defined as having primary subglottic carcinoma (1.8%). In the subglottic cohort, 68 patients were men (76.4%), and mean age at diagnosis was 68 years (interquartile range: 60-77 years). The 5-year os was 47.2%, and the 5-year lfs was 31.5%. In 13 patients (15%), the primary treatment was laryngectomy, which, compared with primary radiation, did not predict for improved os. No differences in os or lfs were observed during the 15-year study period (os p = 0.42, lfs p = 0.83). Conclusions: The survival of patients with subglottic carcinoma is poor and has remained stable over time (1995-2009). Compared with primary radiation, primary treatment with laryngectomy does not appear to improve os.

The use of standardized order sets to improve adherence to evidence-based postoperative management in major head and neck surgery.

BACKGROUND: Standardized order sets (SOSs) are clinical tools derived from clinical care pathways that have shown improved patient-recovery and economic benefits. The primary objective was to examine the effect of SOSs on adherence to evidence-based postoperative guidelines for laryngectomy patients. METHODS: A retrospective chart review comparing handwritten and SOS-based postoperative physician orders was conducted for consecutive laryngectomies performed (n=70) within a 3-year time period. Orders were analyzed for errors and deviations from evidence-based guidelines. Secondary outcome included complications such as thromboembolic disease, return to operating room, fistula formation, salivary bypass tube, length of hospital stay and death. RESULTS: Approximately 81% of cases utilizing handwritten orders had at least one error (n=36) compared to 38% in the group that used an SOS (n=34) (P<0.0001). Subgroup analyses demonstrated that errors in mechanical deep vein thrombosis prophylaxis (P<0.0001) and antibiotic prophylaxis (P=0.0173) orders were significantly reduced in the SOS group compared to the handwritten group. No significant differences were observed between the two groups for measured postoperative complications (P>0.05) and length of hospital stay (18.6 days in both SOS and handwritten orders groups). CONCLUSIONS: SOSs are associated with reduced errors in postoperative orders. They are important tools to improve adherence to standardized guidelines for surgeries requiring complex postoperative management. Clinical care pathways and Enhanced Recovery After Surgery protocols can use SOSs to ensure appropriate orders are being made.

Transoral robotic surgery vs. radiotherapy for management of oropharyngeal squamous cell carcinoma - A systematic review of the literature.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) with or without concurrent chemotherapy is widely utilized for the treatment of oropharyngeal squamous cell carcinoma (OPSCC). However, due to significant acute and late toxicities there has been increasing interest in minimally invasive surgical approaches, particularly transoral robotic surgery (TORS) in an attempt to preserve patient quality of life while maintaining oncologic outcomes. The aim of this study was to review the current literature in order to compare primary IMRT versus TORS in the management of OPSCC. METHODS: A MEDLINE search was conducted to identify studies reporting on the outcomes of TORS or IMRT in the treatment of OPSCC. Reference lists were also reviewed for relevant articles. Oncologic, functional, and quality of life data is summarized and discussed. RESULTS: One hundred-ninety papers were identified through the MEDLINE search. An additional 52 papers were retrieved by hand searching the reference lists. Ultimately, 44 papers were identified that discussed outcomes after IMRT or TORS for OPSCC. No outcomes from randomized trials were identified. CONCLUSION: No randomized trials comparing TORS versus IMRT to each other were identified. Uncontrolled reports from the current literature suggest comparable oncologic outcomes with TORS compared to IMRT and functional outcomes may be superior. However, the median follow-up was relatively short and the TORS studies included patients with earlier stage OPSCC on average compared to IMRT studies. Prospective, randomized controlled trials and direct, well-matched comparisons are needed to further elucidate the role for TORS in the treatment of oropharyngeal squamous cell carcinoma.

Paediatric aerodigestive foreign bodies: remember the nasopharynx.

INTRODUCTION: Nasopharyngeal foreign bodies are relatively uncommon, compared with other aerodigestive sites. They may mimic a lower airway location, or may be coughed up into the nasopharynx prior to endoscopic evaluation. OBJECTIVE: To describe our experience with nasopharyngeal foreign bodies mimicking a more distal airway location. METHOD: Case series from a tertiary referral children's hospital. RESULTS: We present a series of four children who were initially thought to have a lower aerodigestive tract foreign body (three respiratory, one oesophageal), but who were finally diagnosed with nasopharyngeal foreign body. The concept of panendoscopy at all foreign body removals is suggested as a means to avoid a missed nasopharyngeal foreign body. CONCLUSION: Although nasopharyngeal foreign bodies are uncommon, their rare ability to mimic distal sites mandates a thorough endoscopic approach to ensure that all sites (i.e. larynx, lungs, oesophagus and nasopharynx) are evaluated endoscopically.

Informing research participants of research results: analysis of Canadian university based research ethics board policies.

BACKGROUND: Despite potential benefits of the return of research results to research participants, the TriCouncil Policy Statement (TCPS), which reflects Canadian regulatory ethical requirements, does not require this. The policies of Canadian research ethics boards (REBs) are unknown. OBJECTIVES: To examine the policies of Canadian university based REBs regarding returning results to research participants, and to ascertain if the presence/absence of a policy may be influenced by REB member composition. DESIGN: Email survey of the coordinators of Canadian university based REBs to determine the presence/absence of a policy on return of research results to research participants both during an ongoing study and at conclusion. REB coordinators were asked to return a copy of the policy or guidelines and to describe the member composition of their REB. FINDINGS: Of 50 REBs that were contacted 34 (68%) responded and 22 (64.7%) met the inclusion criteria. Two (9.1%) had a policy that governed the return of research results while on a study, and seven (31.8%) following the completion of a study. Presence of an ethicist or a lawyer on the REB did not influence the presence/absence of such policies. No REBs had specific guidelines describing how participants should be informed of results. CONCLUSIONS: Most REBs did not require researchers to disclose study results to research participants either during or following a study. Thus this study identifies an ethical shortcoming in the conduct of human research in Canada. It has also demonstrated that there are no clear recommendations by REBs to facilitate the return of results to participants following research projects.

New clusters of genes required for gliding motility in Myxococcus xanthus.

Gliding is the directed movement of cells across surfaces which occurs in the absence of external organelles such as flagella. Gliding of the complex prokaryote, Myxococcus xanthus, results from the action of two independent sets of genes known as the A (adventurous motility) and S (social motility) genes. Strains with mutations in both systems (A-S-) do not spread on agar surfaces because both individual and group movement is abolished. To generate regulated, transcriptional fusions with operons including A and S genes, we introduced TN5-lac into A- and S- strains to obtain non-motile A-S::Tn5-lac and A::Tn5-lac S- double mutants. These insertions identify five separate clusters of A genes and three separate clusters of S genes on the M. xanthus genome. Some Tn5-lac insertions map near two of the five previously identified motility gene clusters, but at least five new clusters were identified in this search. Single mutations at only one locus, mglA, block motility; the mglA locus is epistatic to A and S motility genes. A- and S- Tn5-lac insertions were transduced into mgl+ and delta mgl strains. The levels of beta-galactosidase activity produced from each A- or S- Tn5-lac insertion are similar in otherwise isogenic mgl+ and delta mgl strains, showing that MglA does not regulate the transcription of many A and S genes.

Genes required for both gliding motility and development in Myxococcus xanthus.

Myxococcus xanthus cells can glide both as individual cells, dependent on Adventurous motility (A motility), and as groups of cells, dependent upon Social motility (S motility). Tn5-lac mutagenesis was used to generate 16 new A- and nine new S- mutations. In contrast with previous results, we find that subsets of A- mutants are defective in fruiting body morphogenesis and/or myxospore differentiation. All S- mutants are defective in fruiting body morphogenesis, consistent with previous results. Whereas some S- mutants produce a wild-type complement of spores, others are defective in the differentiation of myxospores. Therefore, a subset of the A genes and all of the S genes are critical for fruiting body morphogenesis. Subsets of both A and S genes are essential for sporulation. Three S::Tn5-lac insertions result in surprising phenotypes. Colonies of two S- mutants glide on 'swim' (0.35% agar) plates to form fractal patterns. These S- mutants are the first examples of a bacterium in which mutations result in fractal patterns of colonial spreading. An otherwise wild-type strain with one S- insertion resembles the frz- sglA1- mutants upon development, suggesting that this S- gene defines a new chemotaxis component in M. xanthus.