Comparison of diagnostic accuracy of computed tomography virtual endoscopy and flexible fibre-optic laryngoscopy in the evaluation of neck anatomic structures and neoplasms.

BACKGROUND AND PURPOSE: Computed tomography virtual endoscopy (CT-VE) is a non-invasive technique which allows visualisation of intraluminal surfaces by tridimensional reconstruction of air/soft tissues. The aim of this study was to compare the diagnostic accuracy of CT-VE and flexible fibre-optic laryngoscopy (FFL) in identifying normal neck anatomic structures and pharyngeal and laryngeal lesions. METHODS: Forty-two patients with a history of neck cancer were assessed by two ENT surgeons using FFL and by one neuroradiologist using CT-VE in order to evaluate the visualisation of the epiglottis, vallecula, glossoepiglottic folds, pyriform sinuses, vocal cords and mass pathology. The visualisation of the structures in both modalities was assessed according to the following score: 0 = not visualised, 1 = partial visualisation, 2 = complete and clear visualisation. A weighted kappa coefficient was used to evaluate the inter-observer agreement. McNemar's test was performed to compare the two diagnostic tests. RESULTS: The inter-observer agreement between FFL and CT-VE was fair in the assessment of the vocal cords (k = 0.341); moderate in the assessment of the glossoepiglottic folds (k = 0.418), epiglottis (k = 0.513) and pyriform sinuses (k = 0.477); and substantial in the assessment of the vallecula (k = 0.618) and the tumour (0.740). McNemar's test showed no significant difference between the two tests (p<0.05). CONCLUSION: CT-VE is a non-invasive technique with a diagnostic accuracy comparable to FFL in terms of visualisation of anatomical structures and pharyngeal and laryngeal lesions.

Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells.

AIM: One of the defining features of the liver is the capacity to maintain a constant size despite injury. Extrahepatic stem cells especially bone marrow-derived stem cells are thought to undertake an important role in liver repopulation. This study was carried out to evaluate the outcome of autologous bone marrow-derived hepatocytes transplantation in patients with end-stage liver cell failure due to chronic hepatitis C. METHODS: Forty patients were included, divided into two groups. Group I: 20 patients receiving autologous bone marrow-derived mesenchymal stem cells stimulated to hepatic lineage. They were subdivided into two groups regarding the route of transplantation: intrasplenic (10) and intrahepatic (10). Group II: included 20 patients who received traditional supportive treatment. Patients were followed up using examination, laboratory investigations, abdominal ultrasonography, and evaluated by Child score, Model for End Stage Liver Disease score, fatigue scale, and performance status. RESULTS: The results showed significant improvement in group I regarding ascites, lower limb edema, and serum albumin, over the control group. Group I also showed statistically significant improvement in Child score, Model for End Stage Liver Disease score, fatigue scale, and performance status over the controls. No difference was observed between intrahepatic and intrasplenic groups. CONCLUSION: This study demonstrated the safety and short-term efficacy of autologous bone marrow-derived mesenchymal stem cell injection in liver cell failure. Further study is necessary to standardize the cell dose, determine the life span of the injected cells, and detect the appearance of long-term complications.

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).

PURPOSE: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. METHODS AND MATERIALS: A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. RESULTS: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). CONCLUSION: In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.

Role of NQO1 polymorphisms as risk factors for squamous cell carcinoma of the head and neck.

A case: control study was carried out to determine if inactivating polymorphisms of the NQO1 gene at bases 609 and 465 are associated with altered risk of developing squamous cell carcinoma of the head and neck (SCCHN). Genotyping was carried out by PCR RFLP analysis on whole blood samples. The frequency of the inactive 609T and active 609C forms, and the inactive 465T and active 465C forms, of NQO1 were compared in patient and control groups by a logistic regression analysis and odds ratios (ORs) were calculated. Participants were stratified by tobacco and alcohol use, and genotype distributions in these sub-groups were compared. There were no significant differences in genotype distribution between SCCHN patients and the control population for the base 609 or 465 polymorphisms. There were also no significant differences in genotype distributions between patient and control groups for tobacco and/or alcohol users and non-users. Genotype distributions were similar for SCCHN patients at all disease sites with the exception of the nasopharynx where there was a higher incidence of the 609C:609T and 609T:609T genotypes. These results suggest that individuals having either 609T or 465T alleles generally do not have an altered risk of developing SCCHN.

Quality of life, mucositis, and xerostomia from radiotherapy for head and neck cancers: a report from the NCIC CTG HN2 randomized trial of an antimicrobial lozenge to prevent mucositis.

BACKGROUND: The National Cancer Institute of Canada Clinical Trials Group undertook a multicenter, randomized, double-blind controlled trial of an oral antimicrobial versus placebo to prevent and treat mucositis. We present the quality of life (QOL) analysis for this trial. METHODS: One hundred thirty-eight patients were randomly assigned. QOL data were collected every 2 weeks before, during, and after radiotherapy. The European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) and a Trial Specific Checklist (TSC) were used. RESULTS: The antimicrobial lozenge did not impact QOL. The principal acute side effect of radiotherapy is oral pain, affecting more than 90% of patients. Role function is impacted during treatment, and patients experience fatigue. Appetite was reported to markedly increase during radiotherapy. There was a dramatic and persistent increase in dry mouth. CONCLUSIONS: This study highlights the benefits of combining the EORTC QLQ-30 with an "oral" TSC in a randomized controlled trial and provides valuable baseline data for their use with an objective mucositis scoring system.

Mapping the journey of cancer patients through the health care system. Part 3: An approach to staging.

This is the third in a series of articles relating results from a line of research whose intent was to construct a complete history of patient interactions with the health care system using available data sources for all patients diagnosed in 1990 with a primary breast, colorectal, or lung tumour in Manitoba. This article presents details of the development and application of methods to produce TNM staging data on the roughly 2,000 patients in this population. The operational definitions constructed for this research can be adapted for other tumour sites and data sources. Findings include methods developed to overcome the sometimes ambiguous and inconsistent available documentation, which ultimately produced reliable TNM staging data. Survival data for this population by stage of disease are given.

Mapping the journey of cancer patients through health care system. Part 1: developing the research question.

This is the first in a series of articles relating results from research which constructed a complete history of interactions with the health care system from available data sources for all patients diagnosed in 1990 with primary breast, colorectal, or lung tumours in Manitoba from one year prior to diagnosis through to two years post-diagnosis. This article presents the motivation and genesis for this line of research. The study evolved from the question of "What happens to a person who is diagnosed with cancer?" into a major research endeavour encompassing a broad spectrum of philosophic and clinical research questions. A large interdisciplinary team collaborated on developing operational methods to combine existing data sources into unified cancer patient histories.

Mapping the journey of cancer patients through the health care system. Part 2: Methodological approaches and basic findings.

This is the second in a series of articles from a line of research whose intent was to construct a complete history of interactions with the health care system. This paper provides details of the methods developed to collect and collate the scattered information regarding the event history (trajectory) that a cancer patient experiences in traveling through the Manitoba health care system from one year prior to diagnosis through to two years post-diagnosis. Survival data were obtained through 1994. Basic population data obtained from this work are also presented, including survival information through to four years post-diagnosis. Issues regarding standardized data recording and detail level of clinical events in the chart record are discussed. This part of the research demonstrates that diverse data sources in the health care system can be linked with a high degree of accuracy and completeness of data.

CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines.

BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described.

Association between smoking during radiotherapy and prognosis in head and neck cancer: a follow-up study.

BACKGROUND: The study objective was to confirm a previous finding that patients with stage III/IV squamous head and neck cancer (SHNC) who smoke during radiotherapy (RT) experience reduced survival. METHODS: An observational cohort study. Patients' smoking status was assessed weekly by questionnaire plus blood cotinine. Patients were assessed every 3 to 4 months for survival. Logistic regression and Cox proportional hazards analyses were used to detect the independent contribution of smoking on survival. RESULTS: Of 148 patients, 113 smoked during RT. Blood cotinine and smoking questionnaire responses were highly correlated (Spearman R = .69; p < .0005). Abstainers and very light smokers experienced better survival than light, moderate, and heavy smokers (median, 42 vs 29 months; p = .07). Tumor and nodal status and years smoked were the most important prognostic factors. Smoking during RT was not an independent predictor of survival, but baseline smoking status was (p = .016). CONCLUSION: Smoking status should be documented in all future trials of RT in SHNC to allow for pooled analyses with sufficient power to address this question.

An ex vivo study exploring the diagnostic potential of 1H magnetic resonance spectroscopy in squamous cell carcinoma of the head and neck region.

BACKGROUND: Definitive diagnosis of head and neck cancer is generally made by histopathologic evaluation. Management and prognosis largely depend on accurate and timely diagnosis. We have explored the use of (1)H magnetic resonance spectroscopy in search of a better or complementary diagnostic technique. METHODS: Tumor and adjacent normal tissue specimens (n = 135) from untreated head and neck cancer patients (n = 40) were obtained and subjected to spectroscopic evaluation followed by histopathologic analysis. Data were partitioned into training and test sets and subjected to multivariate analysis. RESULTS: The resonances from taurine, choline, glutamic acid, lactic acid, and lipid were found to have diagnostic potential by our optimal region selection algorithm. Multivariate analysis of the spectral data differentiated between normal and malignant tissues, with an overall accuracy of 92.6% (training set, 97.3%; test set, 87.3%), an overall sensitivity of 93% (test set, 90%), and an overall specificity of 92% (test set, 82.6%). CONCLUSIONS: (1)H magnetic resonance spectroscopy combined with multivariate methods of analysis can distinguish between normal and malignant squamous cell tissue, and this may lead to the development of an objective and noninvasive diagnostic procedure.

A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. PURPOSE: The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. MATERIALS AND METHODS: Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. RESULTS: No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. CONCLUSIONS: This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge.

Statistical classification strategy for proton magnetic resonance spectra of soft tissue sarcoma: an exploratory study with potential clinical utility.

PURPOSE: Histological grading is currently one of the best predictors of tumor behavior and outcome in soft tissue sarcoma. However, occasionally there is significant disagreement even among expert pathologists. An alternative method that gives more reliable and non-subjective diagnostic information is needed. The potential use of proton magnetic resonance spectroscopy in combination with an appropriate statistical classification strategy was tested here in differentiating normal mesenchymal tissue from soft tissue sarcoma. METHODS: Fifty-four normal and soft tissue sarcoma specimens of various histological types were obtained from 15 patients. One-dimensional proton magnetic resonance spectra were acquired at 360 MHz. Spectral data were analyzed by using both the conventional peak area ratios and a specific statistical classification strategy. RESULTS: The statistical classification strategy gave much better results than the conventional analysis. The overall classification accuracy (based on the histopathology of the MRS specimens) in differentiating normal mesenchymal from soft tissue sarcoma was 93%, with a sensitivity of 100% and specificity of 88%.The results in the test set were 83, 92 and 76%, respectively. Our optimal region selection algorithm identified six spectral regions with discriminating potential, including those assigned to choline, creatine, glutamine, glutamic acid and lipid. CONCLUSION: Proton magnetic resonance spectroscopy combined with a statistical classification strategy gave good results in differentiating normal mesenchymal tissue from soft tissue sarcoma specimens ex vivo. Such an approach may also differentiate benign tumors from malignant ones and this will be explored in future studies.