Craniomaxillofacial osteosarcoma - The role of surgical margins.

BACKGROUND: Osteosarcomas (OS) in the craniomaxillofacial (CMF) region are typically diagnosed at later age than long-bone OS, but they are reported to have better 5-year survival. Curative treatment warrants wide surgical resection, which is often not possible in the CMF region. The purpose of this article is to present a nationwide series of CMF in Finland to discuss the role of surgery. PATIENTS AND METHODS: All 21 CMF OS patients managed in Finland from 1992 to 2009 were included. The mean age was 40 years (range 15-72). Data on patient and tumor characteristics, treatment modalities, and survival were recorded. All patients had a minimum follow-up of 5 years or until death. RESULTS: OS was evenly represented in the mandible and maxillary bones, which together constituted 76% of all sites. Surgery with curative intent was carried out in 20 patients. Clear margins were achieved in only five cases. Eight (40%) of these 20 patients died due to OS, and their average survival time was 1.3 years. Seven (35%) out of the 20 patients received radiotherapy due to close/intralesional surgical margins, and four of them did not develop recurrences during the follow-up. CONCLUSIONS: The results suggest that postoperative radiotherapy may alter the prognosis in CMF OS, particularly in cases with close or intralesional margins. This may increase the survival rates achieved by prompt action in performing radical surgery.

Short- and long-term mortality and causes of death after reconstruction of cancers of the head and neck with free flaps.

The use of free flaps to reconstruct cancers of the head and neck is accompanied by appreciable postoperative morbidity and high long-term mortality, but the causes of death and the impact of postoperative complications on survival have not been well studied. We have therefore analysed retrospectively the causes of death and survival of 146 such patients operated on between 2008 and 2016 of whom a total of 62 (43%) had died by the end of 2016. The cause of death was the primary disease in 45 of the 62. The median survival of those who died with the primary cancer as the cause of death did not differ from that of those who died of other causes. In a multivariate Cox model indicators of five-year mortality were male sex, low body mass index (BMI), American Society of Anesthesiologists (ASA) grade more than II, and late medical complications. Neither the size of the tumour nor any operative factors were independent risks for five-year mortality. Ten patients died within six months of operation, all of whom had higher postoperative C-reactive protein concentrations than those who survived for more than six months. The cause of death of most patients who died after free flap operations for head and neck cancer was the primary diagnosis. According to these results, patient-related factors (male sex, ASA grade more than II, low BMI, and low albumin concentration) have an important role in long-term survival, which highlights the importance of careful selection of patients for operative treatment.

Complications and outcome after free flap surgery for cancer of the head and neck.

We retrospectively studied 136 patients who had free flap reconstruction for cancer of the head and neck at a single centre (2008-2015) to evaluate complications, assess factors associated with them, and analyse their impact on outcome. Preoperative and perioperative data, and surgical and medical complications were recorded, and the impact of the complications on duration of hospital stay and survival were assessed. A total of 86 (63%) patients had complications. Compared with those who did not, they had a higher rate of alcohol abuse (21/86, compared with 5/50, p=0.039), longer operations (median (IQR) 565 (458-653 compared with 479 (418-556) minutes, p<0.001), and greater intraoperative loss of blood (725 (400-1150) compared with 525 (300-800) ml, p=0.042). Complications were more common in patients who had fibular flaps and T4 disease (22/86 compared with 4/50, p=0.010; 47/80 compared with 16/47, p=0.015, respectively). Those who had complications also stayed in hospital longer (median (IQR) 9 (7-12) compared with 15 (10-21) days, p<0.001). Cumulative mortality was higher in patients with late complications (those that occurred after the fourth postoperative day) (61% compared with 36%, p=0.004). In conclusion, complications in more than half the patients were related to alcohol abuse, a more complicated intraoperative course, and fibular flaps. Complications were associated with a longer hospital stay, and survival was higher in those who did not have late complications than in those who did.

Recurrent acute otitis media detracts from health-related quality of life.

OBJECTIVE: Acute otitis media causes discomfort to children and inconvenience to their parents. This study evaluated the quality of life in children with recurrent acute otitis media aged less than 24 months. METHODS: Quality of life was evaluated in 149 children aged 10 to 24 months who were referred to the Oulu University Hospital on account of recurrent acute otitis media. The children were treated with or without surgery. Age-matched controls were selected randomly from the general child population. Parents completed the Child Health Questionnaire. RESULTS: The children with recurrent acute otitis media had a significantly poorer quality of life than control children. The control children with a history of a few acute otitis media episodes had a significantly poorer quality of life than those without any such history. The quality of life of the children with recurrent acute otitis media improved during the one-year follow up, regardless of the treatment, but did not reach the same level as healthy children. CONCLUSION: Acute otitis media detracted from quality of life when a generic measure was used. The mode of treatment used to prevent further recurrences of acute otitis media did not influence quality of life improvement.

Incidence and predictors of 30-day cardiovascular complications in patients undergoing head and neck cancer surgery.

Incidence and predictors of peri-operative or post-operative cardiovascular complications in head and neck cancer surgery remain poorly elucidated. In this retrospective study, we investigated the rate and pre-operative risk factors for cardiovascular and cerebrovascular complications. This study included all patients (n = 456) operated for head and neck cancer between 1999 and 2008. Patients' medical records were reviewed and the adjudication of endpoints was performed by adjudication committee. The 30-day incidence of cardiovascular and cerebrovascular complications was 7.2 %. Cardiac mortality at 30 days was 1.0 %. Univariate predictors of MACCE (major adverse cardiac and cerebrovascular events) at the 30-day follow-up were history of myocardial infarction (OR 4.56, 95 % CI 1.73-11.97, p = 0.002); history of heart failure (OR 4.14, 95 % CI 1.32-13.02, p = 0.015); pre-existing coronary artery disease (OR 3.98, 95 % CI 1.75-9.06, p = 0.001); prior aspirin medication (OR 3.73, 95 % CI 1.81-7.71, p < 0.001); prior betablocker medication (OR 3.67, 95 % CI 1.79-7.51, p < 0.001); hypertension (OR 2.55, 95 % CI 1.25-5.19, p = 0.010); and increasing age (OR 1.08, 95 % CI 1.05-1.12, p < 0.001). In a multivariate model, independent predictors of MACCE were pre-existing coronary artery disease (OR 2.45, 95 % CI 1.03-5.80, p = 0.042) and increasing age (OR 1.08, 95 % CI 1.04-1.11, p < 0.001). Patients having surgery for head and neck cancer are at high (>5 %) risk of developing vascular complications. Prior coronary artery disease and increasing age are independent risk factors for MACCE.

Predictive Factors for Medical Consultation for Sore Throat in Adults with Recurrent Pharyngotonsillitis.

Objects. To seek patient- and episode-related factors that associate with medical consultation for acute sore throat because these factors may affect the patient being referred to specialist care and tonsillectomy for recurrent pharyngotonsillitis. Methods. In a secondary analysis of two prior randomised controlled trials, sore throat episodes and medical visits were explored among 156 adult patients referred for tonsillectomy because of recurrent pharyngotonsillitis. Results. The 156 patients (104 females, mean age of 26 years) suffered from 208 acute pharyngotonsillitis episodes during 5-6 months of follow-up. Forty (25%) patients visited a physician, and female gender (adjusted hazard ratio, HR, 3.3; 95% confidence interval 1.4-8.0) and finding of chronically infected tonsils (HR 2.7; 1.2-6.1) were associated with medical consultation. Thirty-six (17%) episodes led to medical consultation during the first 7 days of symptoms. Presence of severe throat pain was related to medical visit (HR 4.3; 1.0-18.5). Conclusions. Even among patients with recurrent pharyngotonsillitis, the acute sore throat episodes were usually mild and only few resulted in medical consultation, with female gender, chronically infected tonsils, and having severe throat pain increasing the consultation rate.

Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47 %) than in the controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA.

A simple novel prognostic model for early stage oral tongue cancer.

The prognostication of patient outcome is one of the greatest challenges in the management of early stage oral tongue squamous cell carcinoma (OTSCC). This study introduces a simple histopathological model for the prognostication of survival in patients with early OTSCC. A total of 311 cases (from Finland and Brazil) with clinically evaluated early stage OTSCC (cT1-T2cN0cM0) were included in this multicentre retrospective study. Tumour budding (B) and depth of invasion (D) were scored on haematoxylin-eosin-stained cancer slides. The cut-off point for tumour budding was set at 5 buds (low <5; high ≥5) and for depth of invasion at 4mm (low <4mm; high ≥4mm). The scores of B and D were combined into one model: the BD predictive model. On multivariate analysis, a high risk score (BD score 2) correlated significantly with loco-regional recurrence (P=0.033) and death due to OTSCC (P<0.001) in early stage OTSCC. The new BD model is a promising prognostic tool to identify those patients with aggressive cases of early stage OTSCC who might benefit from multimodality treatment.

Predictive factors for quality of life after tonsillectomy among adults with recurrent pharyngitis: a prospective cohort study.

OBJECTIVES: To assess health-related quality of life (QoL) and clinical factors predicting it after tonsillectomy among adult patients with recurrent pharyngitis. DESIGN: Prospective cohort design. SETTING: Tertiary referral centre. PARTICIPANTS: Adults (n = 153) who underwent tonsillectomy for recurrent pharyngitis. MAIN OUTCOME MEASURES: QoL 6 months after tonsillectomy measured by the Glasgow Benefit Inventory (GBI). Factors predicting high postoperative QoL were sought using multiple linear regression analysis. RESULTS: Of the 142 patients (93% of all eligible) responding to the GBI questionnaire, 94 (66%) were female; median age was 26 years (range 14-65). GBI Total Scores varied markedly (range -19 to +69), but on average showed improvement (median +27, interquartile range 18-36), most evidently in the GBI Physical Health Score (median +83), after tonsillectomy. Among routinely recorded clinical characteristics, the number of prior pharyngitis episodes, frequent throat pain, untreated dental caries and chronically infected tonsils made up the optimal subset of factors for predicting the GBI Total Score. However, in a random sample of patients (n = 56) for whom preoperative diary-based data were also available, somewhat better predictive ability was achieved based on just two diary items: number of days with throat pain and with fever during the preceding few months (correlation coefficient, r, between observed and fitted scores improved from 0.39 to 0.55). Yet, the precision of even these predictions was still quite low. CONCLUSIONS: Adult patients with recurrent pharyngitis were on average satisfied after tonsillectomy, regardless of the aetiology of the episodes. Clinical factors rather modestly predicted which patients benefited most from the operation.

Alcohol-induced premature permeability in mouse placenta-yolk sac barriers in vivo.

OBJECTIVE: Acute alcohol exposure induces malformation and malfunction of placenta-yolk sac tissues in rodents, reducing the labyrinth zone in the placenta and altering the permeability and fluidity of the cell membrane. During normal mouse placentation the cells line up in an optimal way to form a hemotrichorial placenta where layers II and III are connected through gap junctions. These act as molecular sieves that limit the passage of large molecules. PlGF is a developmentally regulated protein that controls the passage of molecules in the vasculosyncytial membranes and media of large blood vessels in the placental villi. In addition to the chorioallontoic placenta, rodents also have another type of placenta that consists of Reichert's membrane within the trophoblast cell layer on the maternal side and the parietal endodermal cells on the embryonic site. This forms a separate materno-fetal transport system. We study here whether alcohol affects these two placental barriers, leading to placental malfunction that in turn diminishes the nutrient supply to the embryo. STUDY DESIGN: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals at 8.75 days post coitum (dpc). The placentas were collected on 9.5, 11.5 and 14.5 dpc and used for histopathological protein studies. Hemotrichorial cell layer structure interactions through connective tissue and gap junction were analyzed by electron microscopy. The permeability of the feto-maternal barrier was visualized with Evans Blue. RESULTS: VEGF, a permeability inducer, was found to be up-regulated in the mouse placenta after acute alcohol exposure, and permeability was also affected by altered structures in the barriers that separate the feto-maternal blood circulation which destroyed the gap junctions in the hemotrichorial cell layer, reduced the thickness of Reichert's membrane and interfered with with Reichert's trophoblast/Reichert's parietal interaction. These defects together could have caused the permeability malfunction of the placenta-yolk sac tissues as visualized and quantified here by Evans Blue leakage. CONCLUSIONS: An altered PlGF/VEGF ratio together with barrier malformation may contribute to placental malfunction by altering the permeability of the feto-maternal barriers. Further studies are needed in order to show whether premature permeability is involved in the intrauterine growth restriction observed in human FAS embryos.

Factors affecting quality-of-life impact of adult tonsillectomy.

OBJECTIVE: To assess the quality of life of adult patients with recurrent tonsillitis after tonsillectomy, and to determine predictive factors for patient satisfaction. METHODS: In a prospective cohort study, a Glasgow benefit inventory questionnaire was posted to 70 adult patients six months after tonsillectomy for recurrent tonsillitis. Data were obtained on patient characteristics, risk factors, tonsillitis history, and clinical and operative findings. The patients were also assessed using self-completed diary data collection regarding acute symptoms (i.e. fever, throat pain, cough and rhinitis), tonsillitis episodes and visits to a doctor, either three to six months before tonsillectomy or six months after tonsillectomy. Predictive factors were sought for inclusion in the worst 30th percentile of patients (i.e. Glasgow benefit inventory score under 18), regarding post-operative change in quality of life. RESULTS: Sixty-two patients (40 females, 22 males; age range 15-46 years) returned the questionnaire (response rate 89 per cent). The mean total Glasgow benefit inventory score after tonsillectomy was +26 (standard deviation 14). The mean scores for Glasgow benefit inventory subscales were: general health +25 (standard deviation 18), social functioning +5 (standard deviation 14) and physical functioning +55 (standard deviation 23). The only factors associated with low patient satisfaction were a small number of tonsillitis episodes (diary-based data) and days with fever before tonsillectomy. CONCLUSIONS: Adult patients with recurrent tonsillitis seemed to be generally pleased with their tonsillectomy. The more symptoms they had prior to surgery, the greater was their improvement in quality of life. No other patient- or disease-related factors were associated with patient satisfaction.

Nasopharyngeal dimensions in magnetic resonance imaging and the risk of acute otitis media.

BACKGROUND: We have previously found by lateral cephalometry an association between nasopharyngeal anatomy and the risk of acute otitis media (AOM). We evaluate here the association of nasopharyngeal dimensions in magnetic resonance imaging (MRI) with the occurrence of AOM in otherwise healthy children. METHODS: Sixty-one healthy children (mean age 5.7 years, range 3.9-6.9) were recruited from child care centres. The parents filled in a questionnaire on the child's history of ear infections and adenoidectomy. MRI was performed with a 4 mm slice thickness during an upper respiratory infection. Five dimensions and two angles expressing the structure of the bony nasopharynx were measured in sagittal images. RESULTS: The dimension from the caudal edge of the septum to the midpoint of the sella, reflecting the height of the nasopharynx, was on average 2.2 mm smaller in the children who had had AOM attacks during the last 12 months than those without attacks (95% confidence interval (CI) 0.9 to 3.4, p=0.001) and the nasal base angle was on average 2.1 degrees smaller (95% CI 0.7 to 3.5, p=0.004). These differences remained significant after adjustment for age, sex and previous adenoidectomy in the logistic modelling. A history of adenoidectomy did not have any effect on the dimensions. CONCLUSIONS: The nasopharynx was smaller in the children with AOM attacks during the last year. The value of this finding for predicting susceptibility to recurrent AOM and directing preventive procedures should be evaluated.

Impact of patient and professional diagnostic delays on the risk of recurrence in laryngeal carcinoma.

OBJECTIVES: To evaluate the impact of patient and professional diagnostic delays on the risk of recurrence in laryngeal squamocellular carcinoma (LSCC). DESIGN: Retrospective study using primary health care records completed before the diagnosis of malignancy. SETTING: One primary health care district (onset of symptoms), one tertiary centre (final diagnosis). PARTICIPANTS: A population-based sample of 99 patients, of which 66 fulfilled the entry criteria, with LSCC diagnosed in northern Finland in 1990-1995. MAIN OUTCOME MEASURES: Impact of patient delay (interval between the onset of symptoms and the first visit to a physician) and professional delay (interval between the first medical visit and histologically verified diagnosis) on the risk of local, neck and distant recurrence in LSCC. RESULTS: Professional delay of 1 year or longer was an independent predictor of both local [adjusted relative hazard (HR) 4.62, P = 0.02] and neck (HR 9.5, P = 0.015) recurrence. Longer professional delay was associated with the risk of recurrence particularly among patients with early stage (stages I-II) disease. Professional delay was almost exclusively because of a delay in referring patients from primary care to an ENT centre. CONCLUSIONS: Lengthened professional diagnostic delay is an independent predictor of an increased risk of local and neck recurrence in early stage LSCC. These patients could benefit from more aggressive primary treatment or more meticulous follow-up.

Cross-sectional survey of paranasal sinus magnetic resonance imaging findings in schoolchildren.

AIM: Sinus image abnormalities are common among children examined for indications other than sinus disease. The purpose of this study was to determine the frequency of sinus abnormalities among otherwise healthy children attending school. METHODS: Magnetic resonance imaging (MRI) was performed on 24 children aged 8-9 y, 18 of whom were re-examined after 6-7 mo. RESULTS: Sinus abnormalities were common. An abnormality was seen in 12 of the children [50%, 95% confidence interval (95% CI) 29-71%], and 9 (38%, 95% CI 19-59%) had abnormalities in the maxillary sinuses. As many as 8 (42%, 95% CI 20-67%) of the asymptomatic children (lacking clinical symptoms or findings) had abnormalities in the maxillary or ethmoidal sinuses. The follow-up examination showed that about half of the abnormal sinus MRI findings had resolved or improved without any intervention. CONCLUSION: Abnormal sinus MRI findings are common both among otherwise healthy children attending school and in totally asymptomatic children. As incidental findings, these should be interpreted as normal and do not indicate any need for treatment in children imaged for purposes other than sinus disease.

The impact of patient and professional diagnostic delays on survival in pharyngeal cancer.

BACKGROUND: Cancers of the head and neck still are detected mostly at an advanced stage, especially pharyngeal cancers. METHODS: To study the impact of patient and professional delay on survival, the authors collected the data from 84 patients with pharyngeal cancer. In addition to clinical data from the tertiary care center, the authors evaluated the data from the first medical visit in primary care before the diagnosis of malignancy had been made. RESULTS: The patients who had a patient delay of 2 months or more had a significantly higher relative hazard of death (HR; HR, 2.5; 95% confidence interval (CI), 1.39-4.38) compared with the patients with less than 2 months of patient delay. This risk was significant among the patients with oropharyngeal (P = 0.008) and nasopharyngeal cancer (P = 0.03), but not in those with hypopharyngeal cancer (P = 0.56). In contrast, there was no relation between professional diagnostic delay and prognosis. Advanced stage (International Union Against Cancer [UICC] TNM; Stage IV vs. Stage I-III; HR, 3.19; CI, 1.61-6.35) and age (> or = 65 vs. < 65 years; HR, 2.47; CI, 1.32-4.62) also were associated with an impaired prognosis. CONCLUSIONS: Shortening of patient delay would substantially improve survival in pharyngeal cancer, but this goal seems difficult to attain because symptoms emerge late in pharyngeal cancer, and no specific symptoms or patient characteristics were related to a long patient delay. Professional delay does not have an impact on survival in pharyngeal cancer.

Post-tonsillectomy pain: a prospective, randomised and double-blinded study to compare an ultrasonically activated scalpel technique with the blunt dissection technique.

Thirty-two patients participated in a study to compare the use of an ultrasonically activated scalpel (Harmonic scalpel) for tonsillectomy on one side and a blunt dissection tonsillectomy on the other. Pain scores at rest and on swallowing expressed as the area under curves (AUC) during the 10 h after surgery, intra-operative blood loss and the need for electrocoagulation for haemostasis were significantly higher on the blunt dissection side than on the Harmonic scalpel side (p < 0.05). However, pain scores expressed as AUC at rest, on swallowing, the day's least, average and worst levels of pain, and the day's worst otalgia during the second week after surgery were significantly higher on the Harmonic scalpel side than on the blunt dissection side. In conclusion, we found that Harmonic scalpel tonsillectomy was associated with decreased severity in pharyngeal pain on the day of the operation but increased pharyngeal pain and otalgia during the second postoperative week.

Secretion of carbonic anhydrase isoenzyme VI (CA VI) from human and rat lingual serous von Ebner's glands.

Salivary carbonic anhydrase VI (CA VI) appears to contribute to taste function by protecting taste receptor cells (TRCs) from apoptosis. The serous von Ebner's glands locating in the posterior tongue deliver their saliva into the bottom of the trenches surrounding the TRC-rich circumvallate and foliate papillae. Because these glands deliver their saliva directly into the immediate vicinity of TRCs, we investigated whether CA VI is secreted by the von Ebner's glands, using immunochemical techniques. The immunohistochemical results showed that CA VI is present in the serous acinar cells, ductal cells, and ductal content of von Ebner's glands and in the demilune and ductal cells plus ductal content of rat lingual mucous glands. More importantly, CA VI was also detected in taste buds and in the taste pores. Western blotting of saliva collected from the orifices of human von Ebner's glands and CAs purified from rat von Ebner's glands confirmed that CA VI is expressed in these glands and secreted to the bottom of the trenches surrounding the circumvallate and foliate papillae. These findings are consistent with the hypothesis that locally secreted CA VI is implicated in the paracrine modulation of taste function and TRC apoptosis. (J Histochem Cytochem 49:657-662, 2001)

Domains b' and a' of protein disulfide isomerase fulfill the minimum requirement for function as a subunit of prolyl 4-hydroxylase. The N-terminal domains a and b enhances this function and can be substituted in part by those of ERp57.

Protein disulfide isomerase (PDI) is a modular polypeptide consisting of four domains, a, b, b', and a', plus an acidic C-terminal extension, c. PDI carries out multiple functions, acting as the beta subunit in the animal prolyl 4-hydroxylases and in the microsomal triglyceride transfer protein and independently acting as a protein folding catalyst. We report here that the minimum sequence requirement for the assembly of an active prolyl 4-hydroxylase alpha(2)beta(2) tetramer in insect cell coexpression experiments is fulfilled by the PDI domain construct b'a' but that the sequential addition of the b and a domains greatly increases the level of enzyme activity obtained. In the assembly of active prolyl 4-hydroxylase tetramers, the a and b domains of PDI, but not b' and a', can in part be substituted by the corresponding domains of ERp57, a PDI isoform that functions naturally in association with the lectins calnexin and calreticulin. The a' domain of PDI could not be substituted by the PDI a domain, suggesting that both b' and a' domains contain regions critical for prolyl 4-hydroxylase assembly. All PDI domain constructs and PDI/ERp57 hybrids that contain the b' domain can bind the 14-amino acid peptide Delta-somatostatin, as measured by cross-linking; however, binding of the misfolded protein "scrambled" RNase required the addition of domains ab or a' of PDI. The human prolyl 4-hydroxylase alpha subunit has at least two isoforms, alpha(I) and alpha(II), which form with the PDI polypeptide the (alpha(I))(2)beta(2) and (alpha(II))(2)beta(2) tetramers. We report here that all the PDI domain constructs and PDI/ERp57 hybrid polypeptides tested were more effectively associated with the alpha(II) subunit than the alpha(I) subunit.