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1.
Oral Oncol ; 49(9): 950-955, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23602256

ABSTRACT

OBJECTIVES: The incidences of hypo(para)thyroidism were assessed prospectively in 137 consecutive patients with laryngeal (84.7%) or hypopharyngeal (15.3%) carcinoma who were treated with surgery and/or radiotherapy between 2004 and 2006. MATERIAL AND METHODS: Laboratory studies were performed in patients before primary or salvage treatment of a laryngeal or hypopharyngeal carcinoma and were repeated 6, 12, 18 and 24months after treatment. All patients were evaluated for the development of hypo(para)thyroidism, and the presence of autoantibodies. The association of hypothyroidism was analyzed against several patient parameters including tumor and treatment characteristics. RESULTS: The incidence of hypothyroidism following treatment of laryngeal and hypopharyngeal carcinoma was 47.4%: 27.7% subclinical hypothyroidism and 19.7% clinical hypothyroidism. The median time to develop hypothyroidism was 10months. The incidence of hypoparathyroidism was 7.3%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, neck dissection, paratracheal lymph node dissection and radiotherapy had a higher risk of developing hypothyroidism. Multivariate analysis showed laryngectomy, hemithyroidectomy, neck dissection and age to be predictive factors for the development of hypothyroidism. The combination of surgery and radiotherapy increased this risk. Hemithyroidectomy was the most important risk factor. CONCLUSION: The incidence rate of hypothyroidism after treatment for laryngeal or hypopharyngeal cancer in this largest prospective study is high (47.4%), especially after combination treatment. Based on the intervals between treatment and the development of hypothyroidism, thyroid testing before treatment, every 3months during the first year, every 6months the second year and annually thereafter is recommended as screening procedure.


Subject(s)
Endocrine Glands/physiopathology , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/surgery , Female , Humans , Longitudinal Studies , Male , Prospective Studies
2.
Oral Oncol ; 49(2): 157-64, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22967965

ABSTRACT

OBJECTIVES: Management of the clinically N0 neck in oral cancer patients remains controversial. We describe the outcome of patients with T1-T2 oral cancer and N0 neck based on ultrasound guided fine needle aspiration cytology (USgFNAC) who were treated by transoral excision and followed by a 'wait and scan' policy (W&S). PATIENTS AND METHODS: This retrospective analysis included 285 consecutive patients of whom 234 were followed by W&S and 51 underwent elective neck dissection (END). Survival rates were compared between groups and correction for confounding factors was performed. RESULTS: Of W&S patients, the 5-year disease-specific (DSS) and overall survival (OS) were 94.2% and 81.6% respectively. During follow-up 72.2% remained free of lymph node metastases and 27.8% developed delayed metastases. W&S patients with delayed metastases had a 5-year DSS and OS of 80.0% and 62.8%, respectively. In patients with positive END these rates were 81.3% and 64.2%, respectively. Between the groups, survival rates were not significantly different. Of the W&S patients with delayed metastases, 90.6% needed adjuvant radiotherapy versus 55.0% of patients with positive END. CONCLUSION: With regard to survival, in patients with early stage oral cancer and cN0 neck a 'wait and scan' policy using strict USgFNAC surveillance is justified as survival is not negatively influenced. Using a 'wait and scan' follow-up strategy instead of elective neck treatment, unnecessary neck dissection and its accompanying morbidity can be avoided in 72.2% of patients. However, for the small proportion of patients with delayed metastases, more extensive treatment with adjuvant radiotherapy is needed.


Subject(s)
Biopsy, Needle/methods , Mouth Neoplasms/surgery , Female , Humans , Lymphatic Metastasis , Male , Mouth Neoplasms/pathology , Mouth Neoplasms/radiotherapy , Observation , Retrospective Studies , Survival Rate , Treatment Outcome , Ultrasonography
3.
Virchows Arch ; 461(6): 629-38, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23064619

ABSTRACT

For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55 ± 0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5 % of the biopsies. A high concordance was observed between hematoxylin-eosin-based consensus diagnosis (≥8/11 readings concordant) and IHC markers. In all cases with EGFR (n = 1) and KRAS (n = 20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Immunohistochemistry/methods , Lung Neoplasms/pathology , Membrane Proteins/analysis , Proto-Oncogene Proteins/genetics , Transcription Factors/analysis , ras Proteins/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , DNA Mutational Analysis , Eosine Yellowish-(YS) , Hematoxylin , Humans , Prospective Studies , Proto-Oncogene Proteins p21(ras) , Reproducibility of Results , Staining and Labeling
4.
Acta Paediatr ; 101(8): 862-7, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22548641

ABSTRACT

AIM: Children with Down syndrome (DS) experience respiratory tract infections (RTIs) more frequently than healthy children. We investigated whether this is related to different immunological characteristics associated with DS. METHODS: The study group consisted of 22 children with DS and 22 of their healthy, age-range matched siblings. Data were collected on infections and hospitalizations because of lower RTIs. Immunoglobulin and IgG subclass levels in blood, as well as lymphocyte and T cell (subset) counts, were determined. RESULTS: The children with DS had a significantly higher frequency of lower RTIs and related hospitalization than their siblings. We also found significantly reduced IgG2 levels as well as significantly lower counts of total lymphocytes, CD4(+) T lymphocytes, CD4(+) invariant natural killer (iNKT) cells and regulatory T cells in the DS group. CONCLUSION: In children with DS, reduced levels of IgG2, total lymphocytes, T lymphocytes, iNKT cells and regulatory T cells might contribute to their higher susceptibility to lower RTIs.


Subject(s)
Adaptive Immunity , Down Syndrome/immunology , Respiratory Tract Infections/immunology , Biomarkers/blood , CD4-Positive T-Lymphocytes/metabolism , Case-Control Studies , Child , Down Syndrome/complications , Female , Heart Defects, Congenital/complications , Heart Defects, Congenital/immunology , Hospitalization/statistics & numerical data , Humans , Immunoglobulin G/blood , Lymphocyte Count , Male , Natural Killer T-Cells/metabolism , Respiratory Tract Infections/complications , Respiratory Tract Infections/epidemiology , Siblings
5.
J Tissue Eng Regen Med ; 6(7): 570-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21916017

ABSTRACT

Apart from soluble growth factors, various other biophysicochemical cues are known to promote chondrogenesis. Under physiological conditions, cartilage in the joint comprises a hyperosmotic and hypoxic environment. Therefore, in this study, we examined the inductive effects of hyperosmotic and/or hypoxic conditions on adipose stem cells (ASCs) and compared them with conventional TGFß1-induction. After encapsulation in collagen type II hydrogels and specific induction, ASCs were assessed for viability, proliferation, morphology and chondrogenic differentiation potential. Viability was similar under all conditions, with low proliferative activity. After 4 days, hypoxia and/or hyperosmolarity did not affect round cell morphology, while cells were mainly stretched in the TGFß1-induced group. At 21 days, the TGFß1-treated group had aggregated into a cell nodule. Hyperosmolarity mimicked this aggregation to a lesser extent, whereas cells under hypoxia stretched out after 21 days, with a combined effect in the hypoxic/hyperosmotic group. Both individual and combined hyperosmotic and/or hypoxic conditions significantly upregulated SOX5, SOX9, COMP and Link-p gene expression compared with the non-induced group, and to similar levels as the TGFß1-induced group. GAG synthesis in both hydrogel and medium was increased under hypoxic conditions, whereas hyperosmolarity decreased GAG formation in the hydrogels, but increased GAG formation in the medium. We conclude that in a joint mimicking the three-dimensional (3D) micro-environment, a combination of hyperosmolarity and hypoxia is able to induce chondrogenesis to the same extent as TGFß1. This might lead to an interesting alternative when considering short-term triggering in a one-step surgical procedure for the treatment of cartilaginous defects.


Subject(s)
Adipose Tissue/cytology , Chondrogenesis/drug effects , Collagen Type II/pharmacology , Hydrogel, Polyethylene Glycol Dimethacrylate/pharmacology , Stem Cells/cytology , Animals , Cell Hypoxia/drug effects , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , Cells, Cultured , Chickens , Chondrogenesis/genetics , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Osmolar Concentration , Staining and Labeling , Stem Cells/drug effects , Stem Cells/metabolism , Stress, Mechanical , Transforming Growth Factor beta1/pharmacology
6.
J Voice ; 26(3): 398-401, 2012 May.
Article in English | MEDLINE | ID: mdl-21840168

ABSTRACT

OBJECTIVE: The purpose of the present pilot study is to investigate whether the beneficial short-term effects of voice therapy in patients with voice problems after treatment of early glottic cancer as reported in our earlier study remain present on the long term. STUDY DESIGN: In this prospective study, 12 patients, selected based on a screening questionnaire about voice problems and randomly assigned for treatment with voice therapy (vs no treatment), were evaluated with a mean of 13 months after finishing voice therapy to evaluate the long-term voice effects. METHODS: Voice assessment consisted of the Voice Handicap Index (VHI) and acoustic analyses (percent jitter, percent shimmer, and noise-to-harmonics ratio). RESULTS: Statistical analysis showed that the beneficial short-term effect on the mean VHI, percent jitter, and shimmer remained stable after more than a year of follow-up. CONCLUSIONS: The present study provides initial evidence that the beneficial effect of voice therapy is not just a short-lived voice improvement but may result in a better voice for a period of at least 1 year. Future long-term randomized controlled trials are needed to confirm our findings.


Subject(s)
Glottis , Laryngeal Neoplasms/therapy , Laryngoscopy/adverse effects , Radiation Injuries/therapy , Voice Disorders/therapy , Voice Quality , Voice Training , Adult , Aged , Aged, 80 and over , Disability Evaluation , Early Detection of Cancer , Glottis/pathology , Glottis/physiopathology , Glottis/radiation effects , Glottis/surgery , Humans , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/physiopathology , Middle Aged , Netherlands , Pilot Projects , Predictive Value of Tests , Prospective Studies , Radiation Injuries/diagnosis , Radiation Injuries/etiology , Radiation Injuries/physiopathology , Speech Production Measurement , Surveys and Questionnaires , Time Factors , Treatment Outcome , Voice Disorders/diagnosis , Voice Disorders/etiology , Voice Disorders/physiopathology , Voice Quality/radiation effects
7.
Int J Audiol ; 50(12): 887-96, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21929374

ABSTRACT

OBJECTIVE: To determine the possible longitudinal relationships between hearing status and depression, and hearing status and loneliness in the older population. DESIGN: Multiple linear regression analyses were used to assess the associations between baseline hearing and 4-year follow-up of depression, social loneliness, and emotional loneliness. Hearing was measured both by self-report and a speech-in-noise test. Each model was corrected for age, gender, hearing aid use, baseline wellbeing, and relevant confounders. Subgroup effects were tested using interaction terms. STUDY SAMPLE: We used data from two waves of the Longitudinal Aging Study Amsterdam (2001-02 and 2005-06, ages 63-93). Sample sizes were 996 (self-report (SR) analyses) and 830 (speech-in-noise test (SNT) analyses). RESULTS: Both hearing measures showed significant adverse associations with both loneliness measures (p < 0.05). However, stratified analyses showed that these effects were restricted to specific subgroups. For instance, effects were significant only for non-hearing aid users (SR-social loneliness model) and men (SR and SNT-emotional loneliness model). No significant effects appeared for depression. CONCLUSIONS: We found significant adverse effects of poor hearing on emotional and social loneliness for specific subgroups of older persons. Future research should confirm the subgroup effects and may contribute to the development of tailored prevention and intervention programs.


Subject(s)
Depression/etiology , Hearing Loss/psychology , Loneliness , Aged , Aged, 80 and over , Depression/epidemiology , Female , Hearing Loss/epidemiology , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Netherlands/epidemiology
8.
Logoped Phoniatr Vocol ; 36(4): 168-74, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21864051

ABSTRACT

OBJECTIVE: Investigation of applicability of neural network feature analysis of nasalance in speech to assess hypernasality in speech of patients treated for oral or oropharyngeal cancer. PATIENTS AND METHODS: Speech recordings of 51 patients and of 18 control speakers were evaluated regarding hypernasality, articulation, intelligibility, and patient-reported speech outcome. Feature analysis of nasalance was performed on /a/, /i/, and /u/ and on the entire stretch of speech. RESULTS: Nasalance distinguished significantly between patients and controls. Nasalance in /a/ and /i/ predicted best intelligibility, nasalance in /a/ predicted best articulation, and nasalance in /i/ and /u/ predicted best hypernasality. CONCLUSION: Feature analysis of nasalance in oral or oropharyngeal cancer patients is feasible; prediction of subjective parameters varies between moderate and poor.


Subject(s)
Mouth Neoplasms/therapy , Neural Networks, Computer , Oropharyngeal Neoplasms/therapy , Phonation , Signal Processing, Computer-Assisted , Speech Production Measurement , Voice Quality , Adult , Aged , Case-Control Studies , Feasibility Studies , Female , Humans , Male , Middle Aged , Mouth Neoplasms/physiopathology , Netherlands , Oropharyngeal Neoplasms/physiopathology , Phonetics , Sound Spectrography , Speech Intelligibility , Treatment Outcome , Young Adult
9.
Diabetes Care ; 34(8): 1843-7, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21700921

ABSTRACT

OBJECTIVE: The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA(1c) and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-HbA(1c) relationship. RESEARCH DESIGN AND METHODS: Analyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-HbA(1c) relationship. RESULTS: GV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-HbA(1c) relationship in type 1 diabetic patients so that high GV led to a higher HbA(1c) level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the HbA(1c) level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency. CONCLUSIONS: In only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with HbA(1c). This effect is more pronounced at higher HbA(1c) levels. However, the impact of GV on the HbA(1c) level in type 1 diabetes is modest, particularly when HbA(1c) is close to the treatment target of 7%.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Glycated Hemoglobin/metabolism , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult
10.
Pediatr Nephrol ; 26(8): 1241-6, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21533870

ABSTRACT

Nephrotic syndrome (NS) is a clinical diagnosis with proteinuria, hypoalbuminaemia and oedema. NS is rare in children, and its incidence in The Netherlands is unknown. The aim of this study was to estimate the incidence of idiopathic NS in the Netherlands. All paediatric patients (age 0-18 years) with a newly diagnosed NS in the Netherlands were registered by the Dutch Pediatric Surveillance Unit during the years 2003 until 2006, secondary NS was excluded. All paediatricians filled out questionnaires about the first clinical findings of the patients and incidences were calculated. A literature review on incidences of childhood NS was conducted. The incidence of NS in children in the Netherlands in the years 2003 until 2006 was 1.52/ 100, 000 children/ year. The median age at diagnosis was 3.88 years with a mean age of 5.08 years. A significant male:female ratio of 2.04:1 was found. This prospective study of NS in the Netherlands revealed an incidence of 1.52:100, 000 children/year, and is similar to the incidences found all over the world.


Subject(s)
Nephrotic Syndrome/epidemiology , Adolescent , Age of Onset , Child , Child, Preschool , Cohort Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Netherlands/epidemiology
11.
Clin Cancer Res ; 17(11): 3733-41, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21467160

ABSTRACT

PURPOSE: TP53 is a key gene in cellular homeostasis and is frequently mutated in head and neck squamous cell carcinoma (HNSCC). There is a variety of TP53 mutations, each with its own biological and clinical implication. Aim of the study was to assess the prognostic significance of TP53 mutations in HNSCCs and to identify the most relevant mutation. EXPERIMENTAL DESIGN: TP53 mutation status was investigated in 141 consecutive HNSCCs treated by surgery with radiotherapy when indicated and with a known human papilloma virus status. The type of mutation was correlated with overall and progression-free survival in a multivariate two-sided Cox regression analysis with wild type as reference. RESULTS: A TP53 mutation was found in 88 (62.4%) of the carcinomas and was not significantly associated with overall survival (HR = 1.65, P = 0.11). Patients with a mutation resulting in a truncated protein (n = 36, 25.5%) had a significantly worse overall survival (HR = 2.54, P = 0.008) and progression-free survival (HR = 2.65, P = 0.002). Four of these mutations were at a splice site, 13 were nonsense mutations (produces stop codon), and 19 were insertions or deletions resulting in a frameshift. After multivariate analysis, a truncating mutation remained a significant prognosticator. A missense (i.e., nontruncating) mutation did not influence prognosis. Other ways of classification (disruptive vs. nondisruptive, hotspot vs. nonhotspot, and DNA binding vs. non-DNA binding) were less discriminative. CONCLUSION: In HNSCCs, a truncating TP53 mutation is associated with a poor prognosis. This patient group seems as a target population for adjuvant therapy with chemoradiation or viral vector-mediated TP53 gene transfer.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/genetics , Mutation , Tumor Suppressor Protein p53/genetics , Female , Humans , Male , Prognosis
12.
World J Gastroenterol ; 17(4): 506-13, 2011 Jan 28.
Article in English | MEDLINE | ID: mdl-21274381

ABSTRACT

AIM: To evaluate cladribine [2-chlorodeoxyadenosine (2-CdA)] therapy in refractory celiac disease (RCD) II. METHODS: An open-label cohort-study of RCD II patients treated with 2-CdA was performed between 2000 and 2010. Survival rate, enteropathy associated T-cell lymphoma (EATL) occurrence, clinical course, and histological and immunological response rates were evaluated. RESULTS: Overall, 32 patients were included with a median follow-up of 31 mo. Eighteen patients responded well to 2-CdA. Patients responsive to 2-CdA had a statistically significant increased survival compared to those who were unresponsive. The overall 3- and 5-year survival was 83% in the responder and 63% and 22% in the non-responder group, respectively. The overall 2-year clinical, histological and immunological response rates were 81%, 47% and 41%, respectively. Progression into EATL was reported in 16%, all of these patients died. CONCLUSION: Treatment of RCD II with 2-CdA holds promise, showing excellent clinical and histological response rates, and probably less frequent transition into EATL.


Subject(s)
Celiac Disease/drug therapy , Celiac Disease/pathology , Celiac Disease/physiopathology , Cladribine/therapeutic use , Immunosuppressive Agents/therapeutic use , Adult , Aged , Cohort Studies , Disease Progression , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Remission Induction
13.
Dig Liver Dis ; 43(2): 110-5, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20739231

ABSTRACT

BACKGROUND: Thioguanine has been used for the treatment of inflammatory bowel disease, in particular for patients who failed conventional thiopurine therapy. To date, thioguanine has been infrequently studied in ulcerative colitis. AIM: To evaluate the tolerability, safety and efficacy of thioguanine in the treatment of ulcerative colitis. METHODS: A database analysis was performed on inflammatory bowel disease patients who had failed conventional thiopurine therapy and were treated with thioguanine. Rates and reasons for treatment failure were assessed. Laboratory values, abdominal ultrasonography, liver biopsy and endoscopic remission rates were evaluated. RESULTS: Forty-six patients were included and median treatment duration was 22 months (range 0.3-72.0). Nine patients failed thioguanine therapy: six due to adverse events, three due to therapy resistance. Concomitant treatment with aminosalicylates protected against thioguanine failure (hazard ratio (HR) 0.11, 95% CI 0.03-0.48). When performed, ultrasonography (n = 21) revealed no suspected therapy-related pathology in all but one patient, in whom hepatomegaly was observed. Liver histology (n = 12) predominantly revealed no abnormalities (n = 4) or non-specific regeneration (n = 4); none showed nodular regenerative hyperplasia. At follow-up, 40% of colonoscopies revealed endoscopic remission as compared with 10% at baseline (P = 0.180). CONCLUSIONS: Long-term use of thioguanine appears to be well tolerated and relatively safe in ulcerative colitis patients who failed conventional thiopurine therapy.


Subject(s)
Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/administration & dosage , Thioguanine/administration & dosage , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Colitis, Ulcerative/diagnosis , Databases, Factual , Drug Therapy, Combination , Female , Follow-Up Studies , Gastrointestinal Agents/adverse effects , Humans , Male , Middle Aged , Netherlands , Odds Ratio , Thioguanine/adverse effects , Time Factors , Treatment Outcome
14.
Int J Cancer ; 128(8): 1852-9, 2011 Apr 15.
Article in English | MEDLINE | ID: mdl-20568113

ABSTRACT

A major problem in head and neck cancer surgery is the high rate of local relapse (LR). In at least 25% of the surgically treated head and neck squamous cell carcinoma (HNSCC) patients, a genetically defined preneoplastic lesion, also known as "field," can be detected in the surgical margins. A remaining field may be an important cause for the development of LR. The aims of our study are (i) to investigate whether HNSCC patients with an unresected field are more likely to develop LR, and (ii) to identify molecular risk factors that predict malignant transformation of field. We retrospectively studied 35 HNSCC patients of whom 16 patients developed LR and 19 patients remained disease-free for at least 4 years. Loss of heterozygosity (LOH) at chromosomes 3p, 9p and 17p, p53 immunostaining, Ki-67 immunostaining and histopathological grading of all available paraffin-embedded surgical margins was performed, and related to LR. Significant associations were determined by Kaplan-Meier analysis and Cox-proportional hazard models. We show that presence of field is significantly associated with LR and that LOH at 9p and p53 immunostaining have the most predictive potential (hazard ratios 3.17 and 3.46, and p values 0.027 and 0.017, respectively). The combination of LOH at 9p and/or a large p53 positive field is most predictive (hazard ratio 7.06 and p = 0.01). Presence and grade of dysplasia was not associated with LR. These data may have major impact for future diagnostic workup of surgically treated HNSCC patients.


Subject(s)
Carcinoma, Squamous Cell/pathology , Chromosomes, Human, Pair 9/genetics , Head and Neck Neoplasms/pathology , Loss of Heterozygosity , Neoplasm Recurrence, Local/diagnosis , Tumor Suppressor Protein p53/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 3/genetics , DNA, Neoplasm/genetics , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/surgery , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/surgery , Polymerase Chain Reaction , Prognosis
16.
Am J Clin Nutr ; 92(5): 1151-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20881073

ABSTRACT

BACKGROUND: Plasma arginine concentrations are lower in patients with cancer, which indicates that arginine metabolism may be disturbed in these patients. Arginine supplementation has been associated with positive effects on antitumor mechanisms and has been shown to reduce tumor growth and to prolong survival. Furthermore, the prognosis of patients with head and neck cancer remains disappointing. Insufficient intake frequently leads to malnutrition, which contributes to high morbidity and mortality rates. OBJECTIVE: The aim of this study was to assess the long-term effects of perioperative arginine supplementation in severely malnourished patients with head and neck cancer. DESIGN: In this double-blind, randomized, controlled trial, we randomly assigned 32 severely malnourished patients with head and neck cancer to receive 1) standard perioperative enteral nutrition (n = 15) or 2) arginine-supplemented perioperative enteral nutrition (n = 17). The primary outcome was long-term (≥10 y) survival. Secondary outcomes included the long-term appearance of locoregional recurrence, distant metastases, and second primary tumors. RESULTS: No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better overall survival (P = 0.019) and better disease-specific survival (P = 0.022). Furthermore, the arginine-supplemented group had a significantly better locoregional recurrence-free survival (P = 0.027). No significant difference in the occurrence of distant metastases or occurrence of a second primary tumor was observed between the groups. CONCLUSION: Perioperative arginine-enriched enteral nutrition significantly improved the long-term overall survival and long-term disease-specific survival in malnourished patients with head and neck cancer.


Subject(s)
Arginine/therapeutic use , Dietary Supplements , Head and Neck Neoplasms/drug therapy , Malnutrition/drug therapy , Secondary Prevention , Aged , Double-Blind Method , Enteral Nutrition , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/secondary , Humans , Male , Malnutrition/etiology , Middle Aged , Perioperative Care , Survival Analysis , Time Factors
17.
Oral Oncol ; 46(9): 672-7, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20656544

ABSTRACT

Radiation may cause radiation-induced cancers after a long latency period. In a group of 111 patients surgically treated for hypopharyngeal carcinoma, patients previously treated with radiotherapy for tuberculosis in the neck were compared to patients without previous radiotherapy. Seven patients (7.4%) underwent radiotherapy (median age 15 years) and developed a hypopharyngeal carcinoma (median age 70 years, median latency period 54.4 year). Considering this long latency period and the localisation in the previous radiation field these tumours can be classified as potentially radiation-induced carcinomas. Patients with potentially radiation-induced carcinomas were significantly older when the hypopharyngeal carcinoma was diagnosed (p=0.048), were more frequently females (p=0.05) and had a worse 5-year regional control rate (p=0.048). When radiotherapy is considered in young patients the risk of induction of tumours has to be kept in mind.


Subject(s)
Carcinoma, Squamous Cell/pathology , Hypopharyngeal Neoplasms/pathology , Neoplasms, Radiation-Induced/pathology , Tuberculosis/radiotherapy , Adolescent , Adult , Aged , Carcinoma, Squamous Cell/etiology , Child , Child, Preschool , Dose Fractionation, Radiation , Female , Humans , Hypopharyngeal Neoplasms/etiology , Kaplan-Meier Estimate , Male , Neck , Time Factors , Young Adult
18.
BMC Med Genet ; 11: 113, 2010 Jul 16.
Article in English | MEDLINE | ID: mdl-20637082

ABSTRACT

BACKGROUND: The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. METHODS/DESIGN: This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. DISCUSSION: This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous parents of affected children compared to the consanguineous parents of healthy children. If our hypothesis proves to be correct, further studies are needed to obtain different risk figure estimates for the different proportions of DNA identical-by-descent. With more precise information about their risk status, empowerment of couples can be improved when making reproductive decisions.


Subject(s)
Chromosome Disorders/genetics , DNA/genetics , Genes, Recessive , Parents , Child , Chromosome Disorders/epidemiology , Chromosome Disorders/mortality , Consanguinity , Female , Genetic Variation , Humans , Male , Pedigree , Prevalence , Reference Values , Risk Assessment , Stochastic Processes
19.
Radiother Oncol ; 97(2): 258-62, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20189668

ABSTRACT

BACKGROUND AND PURPOSE: The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6 months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy. MATERIALS AND METHODS: Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale). RESULTS: Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6 months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning. CONCLUSION: Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer.


Subject(s)
Mouth Neoplasms/radiotherapy , Mouth Neoplasms/surgery , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/surgery , Quality of Life , Adult , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prospective Studies
20.
J Oral Maxillofac Surg ; 68(5): 1094-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20149509

ABSTRACT

PURPOSE: The purpose of this study was to assess temporomandibular function after condylectomy because of unilateral condylar hyperactivity (UCH) by means of standardized diagnostic criteria. The results were compared with those obtained in a control group. PATIENTS AND METHODS: In this study, 33 patients with UCH who underwent condylectomy and 31 controls matched for age and gender filled out a history questionnaire and underwent a clinical examination as part of the research diagnostic criteria for temporomandibular disorders. Data analysis was performed by use of the Fisher exact test for 2-by-2 tables. RESULTS: Patients and controls did not differ significantly regarding myofacial pain (P = .131), disc displacement (P = .516), and depression (P = .34). The groups differed significantly concerning arthralgia, osteoarthritis, and osteoarthrosis (P = .003), as well as pain with low disability (P = .022). CONCLUSIONS: In patients with UCH who underwent condylectomy because of progressive mandibular asymmetry, more joint-related temporomandibular problems as well as more postoperative pain developed when compared with age- and gender-matched controls. However, these problems did not lead to more severe disabilities in daily life.


Subject(s)
Facial Asymmetry/surgery , Mandibular Condyle/surgery , Mandibular Diseases/surgery , Temporomandibular Joint/physiopathology , Adult , Arthralgia/diagnosis , Case-Control Studies , Depression/diagnosis , Facial Pain/diagnosis , Female , Humans , Joint Dislocations/diagnosis , Male , Middle Aged , Osteoarthritis/diagnosis , Osteotomy , Postoperative Complications/diagnosis , Range of Motion, Articular/physiology , Somatoform Disorders/diagnosis , Temporomandibular Joint Disc/physiopathology , Temporomandibular Joint Disorders/diagnosis , Young Adult
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