Association of Picornavirus Infections With Acute Otitis Media in a Prospective Birth Cohort Study.

BACKGROUND: Human rhinoviruses (HRVs), human enteroviruses (HEVs) and human parechoviruses (HPeVs) have been linked to acute otitis media (AOM). We evaluated this association in a prospective birth cohort setting. METHODS: A total of 324 healthy infants were followed up from birth to age 3 years. Nasal swab samples were collected at age 3, 6, 12, 18, 24, and 36 months and screened for HRV and HEV using real-time reverse-transcription quantitative polymerase chain reaction. Stool samples were collected monthly and analyzed for HRV, HEV, and HPeV. AOM episodes diagnosed by physicians were reported by parents in a diary. The association of viruses with AOM was analyzed using generalized estimation equations, and their relative contributions using population-attributable risk percentages. RESULTS: A clear association was found between AOM episodes and simultaneous detection of HEV (adjusted odds ratio for the detection of virus in stools, 2.04; 95% confidence interval, 1.06-3.91) and HRV (1.54; 1.04-2.30). HPeV showed a similar, yet nonsignificant trend (adjusted odds ratio, 1.44; 95% confidence interval, .81-2.56). HRV and HEV showed higher population-attributable risk percentages (25% and 20%) than HPeV (11%). CONCLUSIONS: HEVs and HRVs may contribute to the development of AOM in a relatively large proportion of cases.

Prognostic impact of tumour-stroma ratio in early-stage oral tongue cancers.

AIMS: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi-institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)-stained tumour-resection slides in a series of early-stage (cT1-2N0) OTSCC patients. METHODS AND RESULTS: A TSR cutoff value of 50% was used to divide the patients into stroma-rich (≥50%) and stroma-poor (<50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early-stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma-rich group. In a multivariate analysis, the stroma-rich group had worse disease-free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17-2.79, P = 0.008], and higher cancer-related mortality (HR 1.71, 95% CI 1.02-2.86, P = 0.03). The combination of the highest-risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71-6.82, P = 0.004) and cancer-related mortality (HR 11.63, 95% CI 3.83-35.31, P < 0.001). CONCLUSIONS: We conclude that TSR is a simple histopathological feature that is useful for prognostication of early-stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE-stained slides.

Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland.

BACKGROUND: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period. METHODS: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent. RESULTS: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality. CONCLUSION: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients.

Quality of life after endovascular sclerotherapy of low-flow venous malformations: the efficacy of polidocanol compared with ethanol.

Background Limited information is available on mid-term results and quality of life (QOL) after endovascular sclerotherapy of venous malformations. Purpose To compare two agents-polidocanol and ethanol-with a focus on the influence on QOL after sclerotherapy. Material and Methods Forty-one consecutive patients with a venous malformation in the head and neck area or in the extremities were treated with polidocanol between 2008 and 2013. Pre- and post-treatment magnetic resonance imaging (MRI) scans were compared. All patients completed a self-evaluation form on symptoms as well as a QOL questionnaire. The results were compared with previously obtained material during 1991-2001, comprising 44 consecutive, similarly located venous malformation patients subject to ethanol sclerotherapy. Results No significant clinical complications were observed. Subjectively, 19 (46%) of the patients benefitted from the treatment. QOL results showed that 85% of patients had an index < 39 - where 0 represents the highest and 100 the lowest QOL. Patients in the ethanol group had marginally better overall post-treatment QOL results. Post-treatment MRI in 35 patients showed the size of the malformation unchanged in 19 (54%) patients, in ten (29%) there was a decrease (<50%) while in six (17%) the decrease was more significant (>50%). Post-treatment MRI results did not correlate with either subjective symptoms or QOL results. Conclusion Polidocanol sclerotherapy were found to be an effective, safe, and well tolerated treatment option for low flow venous malformations. Routine MRI for follow-up appears redundant and may be omitted.

Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children.

According to studies based on bacterial cultures of middle ear fluids, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis have been the most common pathogens in acute otitis media. However, bacterial culture can be affected by reduced viability or suboptimal growth of bacteria. PCR detects bacterial DNA from samples with greater sensitivity than culture. In the present study, we analyzed the middle ear pathogens with both conventional culture and semiquantitative real-time PCR in 90 middle ear fluid samples obtained from children aged 5 to 42 months during acute otitis media episodes. Samples were tested for the presence of S. pneumoniae, H. influenzae, M. catarrhalis, Alloiococcus otitidis, Staphylococcus aureus, and Pseudomonas aeruginosa One or more bacterial pathogens were detected in 42 (47%) samples with culture and in 69 (77%) samples with PCR. According to PCR analysis, M. catarrhalis results were positive in 42 (47%) samples, H. influenzae in 30 (33%), S. pneumoniae in 27 (30%), A. otitidis in 6 (6.7%), S. aureus in 5 (5.6%), and P. aeruginosa in 1 (1.1%). Multibacterial etiology was seen in 34 (38%) samples, and M. catarrhalis was detected in most (85%) of those cases. Fifteen signals for M. catarrhalis were strong, suggesting a highly probable etiological role of the pathogen. In conclusion, even though M. catarrhalis is often a part of mixed flora in acute otitis media, a considerable proportion of cases may be primarily attributable to this pathogen.

High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

Utilization of Three-Dimensional Computer-Aided Preoperative Virtual Planning and Manufacturing in Maxillary and Mandibular Reconstruction with a Microvascular Fibula Flap.

BACKGROUND: The aim of this study was to analyze the effects of computer-aided three-dimensional virtual planning and the use of customized cutting guides in maxillary and mandibular reconstruction with a microvascular fibula flap. METHODS: Patients (n = 17) undergoing free fibula flap (n = 18) reconstruction of the maxilla (n = 2) or mandible (n = 15) from January 2012 through March 2014 were enrolled in the study. Preoperatively, patients underwent high-resolution computed tomography of the maxillofacial and lower leg regions. Three-dimensional virtual planning of the resection and reconstruction was performed. Customized cutting guides for maxillary/mandibular resections and fibular osteotomies, and prebend plates were manufactured. Demographic data, surgical factors, and perioperative and postoperative results were evaluated. RESULTS: Sixteen patients had malignant disease and one had benign disease. Sixteen of the flaps were osteomuscular and two were osteomusculocutaneous. Mean ischemia time was 99 minutes and mean operative time was 542 minutes. The flaps fitted into the defects precisely and no bone grafts were needed. Mean length of the fibula flap was 74 mm and the mean number of segments in the flap was 2.1. CONCLUSION: Three-dimensional computer-aided preoperative virtual planning allowed for precise planning of the tumor resection and size of the fibula flap, the number and placement of the osteotomies needed, and the manufacture of customized cutting guides. Fibular shaping is easier and faster, which may decrease the ischemia time and total operative time. Exact placement of the flap in the defect may facilitate restoration of the anatomic shape and ossification.

Efficacy of OK-432 sclerotherapy in treatment of lymphatic malformations: long-term follow-up results.

Lymphatic malformations (LMs) are rare congenital tumors of the lymphatic system often affecting the head and neck area. Because of cosmetic and functional symptoms most patients need to be treated. Traditionally surgical treatment has been considered to be the first-line treatment for LM. However, it is challenging because of the need for complete excision. The risk of poor cosmetic result and damage to surrounding structures is high. Since Ogita presented OK-432 as a treatment for LM in 1987, it has been widely used as the primary treatment. Many papers have been published on this topic but with relatively short follow-up times. We present a material of 36 LMs treated with OK-432 during the period of 1999-2009 and with an average follow-up time of 6 years. Immediate post-treatment results were compared with the late follow-up findings. Primary and late response to therapy was evaluated with an MRI scan by measuring the change in lesion size. At the follow-up visit, all patients were clinically examined and they answered a symptom questionnaire. Later 26/36 patients were also available for a quality of life questionnaire. Primarily 67% demonstrated a complete or marked response. At the follow-up 64% showed a complete or marked response, in 11% the final response was better than the initially observed and only 2 patients had relapsed. The initial response predicted the long-term outcome accurately and the effect of OK-432 sclerotherapy seems to be long lasting. According to the MRI evaluation 80% and subjectively 94% of the patients benefitted from the treatment. Quality of life questionnaire showed high post-treatment satisfaction. We found OK-432 sclerotherapy to be a safe and effective treatment with a long lasting effect in the management of macrocystic LMs.

[Combined technique in the removal of parotid gland stones]. / Yhdistelmätekniikka korvasylkirauhasen kivien poistossa.

Sialendoscopy is used in the diagnostics and treatment of salivary gland swelling. Small intraductal stones can be removed with various instruments during sialendoscopy. In cases with larger fixed stones a combined technique can be applied. The stone is approached endoscopically, skin flap is raised or a small incision is made through the illuminated area and the stone is removed via the external route with minimal morbidity. In this series five out of seven patients treated by the combined technique became symptomless. Superficial parotidectomy was performed on one patient. The combined technique is recommended in the removal of stones that are large, fixed in the duct or located in the gland's hilus.

[Chronic sclerosing sialadenitis - Küttner tumor]. / Krooninen sklerosoiva sylkirauhastulehdus - küttnerin tuumori.

Chronic sclerosing sialadenitis i.e. Küttner tumor is a rare inflammatory disease most commonly affecting the submandibular gland, due to clinical findings easily interpreted even as a malignant tumor. Our 45-year-old patient sought medical care due to a solid lump that had appeared under the right mandibular angle. The submandibular gland and associated hard mass were excised in a surgical operation conducted after the investigations. Histologic examination proved that the seldom diagnosed reactive Küttner tumor was in question.

Sympathetic innervation does not contribute to glycerol release in ischemic flaps.

BACKGROUND: Extracellular glycerol as detected by microdialysis has been used as a surrogate marker for (ischemic) tissue damage and cellular membrane breakdown in the monitoring of free microvascular musculocutaneous flaps. One confounding factor for glycerol as a marker of ischemic cell damage is the effect of lipolysis and associated glycerol release as induced by sympathetic signalling alone. We hypothesized that extracellular glycerol concentrations in a microvascular flap with sympathetic innervation would be confounded by intact innervation per se as compared to denervated flap. Clinical relevance is related to the use of both free and pedicled flaps in reconstructive surgery. We tested the hypothesis in an experimental model of microvascular musculocutaneal flaps. METHODS: Twelve pigs were anesthetized and mechanically ventilated. Two identical rectus abdominis musculocutaneal flaps were raised for the investigation. In the A-flaps the adventitia of the artery and accompanying innervation was carefully stripped, while in the B-flaps it was left untouched. Flap ischemia was induced by clamping both vessels for 60 minutes. The ischemia was confirmed by measuring tissue oxygen pressure, while extracellular lactate to pyruvate ratio indicated the accompanying anaerobic metabolism locally. RESULTS: Intramuscular and subcutaneal extracellular glycerol concentrations were measured by microdialysate analyzer. Contrary to our hypothesis, glycerol concentrations were comparable between the two ischemia groups at 60 minutes (p = 0.089, T-test). CONCLUSIONS: In this experimental model of vascular flap ischemia, intact innervation of the flap did not confound ischemia detection by glycerol. Extrapolation of the results to clinical setting warrants further studies.

A national series of 244 sinonasal cancers in Finland in 1990-2004.

Sinonasal cancer is still a somewhat controversial entity because most series are single-center studies. The aim of this study was to give more accurate and generalisable information about treatment of the neck and prognosis of sinonasal cancer. Retrospective, population-based, multicentre study. Altogether 244 patients diagnosed in 1990-2004 were evaluated. The 3- and 5-year disease-specific survival (DSS) rates after treatment with curative intent were 68 and 57%, respectively. Regional status at the time of the diagnosis (P < 0.001, log rank) and local recurrence (P = 0.02, log rank) during the follow-up had a statistically significant effect on DSS. Initially 13% of the patients were diagnosed with neck metastasis. The proportion of regional recurrences during the follow-up was 9%, but it did not have a statistically significant impact on DSS (P = 0.68, log rank). Histopathology had no statistically significant impact on survival in this material of 244 patients. In conclusion, routine elective neck treatment of all sinonasal cancer patients is not recommended, but the importance of the treatment of the primary location is emphasised.

[Pott's puffy tumor--a rare complication of frontal sinusitis]. / "Pott's puffy"-tuumori--otsaontelotulehduksen harvinainen komplikaatio.

Pott's puffy tumor is an extremely rare complication of frontal sinusitis. It is most typically found in young men. Streptococci, staphylococci or anaerobic bacteria are usually the causative agents. In our patients the inflammation was caused by Streptococcus milleri and Streptococcus pneumoniae. The treatment should be started with broad-spectrum antibiotics. The antibiotics are administered intravenously for 1 to 2 weeks and thereafter orally for at least four weeks. Paranasal sinuses must be operated, and if necessary, intracranial abscesses are treated neurosurgically.

[Current issues in the treatment of pharyngeal cancer]. / Nielusyövän hoidon ajankohtaiset kysymykset.

In Finland over the past few years approximately 100 new cases of oro- and hypopharyngeal cancer have been diagnosed annually. Most of these are squamous cell carcinomas. The incidence of these diseases increases after age 45. Minor and nonspecific local symptoms caused by the primary tumor are common to pharyngeal cancers at the initial stage of the disease. Often the diagnosis is delayed and the search for the primary tumor is begun only after detection of neck metastases. They occur in 60 to 80% at the time of diagnosis. Among the risk factors, smoking and heavy drinking are most important.

[Therapeutic results in oral cancer--what has been learned?]. / Suusyövän hoitotulokset--mitä on opittu?

Oral cancer is the most common head and neck cancer in Finland. The number of new cases has been on a steady rise over the last decades. Smoking and heavy drinking are the most important risk factors. The role of papilloma virus infection is under active research, albeit with a smaller role than in oropharyngeal cancer, for instance. Surgical excision of the tumor is usually the first-line treatment. Pathoanatomical investigation of the primary tumor and cervical lymph nodes is essential in evaluating the need of adjuvant therapy. The prognosis of oral cancer has improved as a result of early detection and development of treatment modalities.

Quality of life and clinical results after endovascular sclerotherapy: A comparison between intra- and extramuscular low-flow venous malformations.

BACKGROUND: Based on clinical observations we hypothesized that patients with intramuscular venous malformations (VMs) did worse or needed more sclerotherapy sessions than patients with extramuscular VMs. PURPOSE: To evaluate the difference in treatment and quality of life (QOL) results after Polidocanol sclerotherapy of intra- and extramuscular low-flow VMs. MATERIAL AND METHODS: Forty-one patients with a VM were treated with Polidocanol in two university hospitals. The results were retrospectively analyzed. Pre- and post-treatment magnetic resonance imaging (MRI) scans were compared. All patients completed a self-evaluating form on symptoms as well as a QOL questionnaire. The results were compared between two groups: intra- and extramuscular VM's. RESULTS: No statistically significant differences between intra- and extramuscular groups concerning QOL and specific dimensions pain, functional problems or cosmetic appearance were found. Radiological changes in MRI examinations did not correlate with any of the subjective symptoms. 56% of the patients benefitted from the treatment according to patient self-evaluation. CONCLUSION: In this material intramuscular VM's responded to the treatment comparably to extramuscular malformations. Post-treatment MRI findings do not correlate with subjective symptoms or QOL results and thus, a routine post-treatment examination seems to be unwarranted. Subjective symptoms and QOL results are the most important parameters in evaluating the effectiveness of sclerotherapy.

Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations.

BACKGROUND: Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients' genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)]. RESULTS: We identified a somatic PIK3CA mutation in resected lesions of 108 out of 143 patients (75.5%). The frequency of the variant allele ranged from 0.54 to 25.33% in tissues, and up to 47% in isolated endothelial cells. We detected a statistically significant difference in the distribution of mutations between patients with common and combined LM compared to the syndromes, but not with KTS. Moreover, the variant allele frequency was higher in the syndromes. CONCLUSIONS: Most patients with an common or combined lymphatic malformation with or without overgrowth harbour a somatic PIK3CA mutation. However, in about a quarter of patients, no such mutation was detected, suggesting the existence of (an)other cause(s). We detected a hotspot mutation more frequently in common and combined LMs compared to syndromic cases (CLOVES and PROS). Diagnostic genotyping should thus not be limited to PIK3CA hotspot mutations. Moreover, the higher mutant allele frequency in syndromes suggests a wider distribution in patients' tissues, facilitating detection. Clinical trials have demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. Genotyping might lead to an increase in efficacy, as treatments could be more targeted, and responses could vary depending on presence and type of PIK3CA-mutation.

Modern postoperative monitoring of free flaps.

PURPOSE OF REVIEW: Flap failure in microvascular reconstruction is a costly complication with total flap loss being the worst-case scenario. With the aim to rapidly identify a postoperative circulatory problem, some susceptible flaps can be saved by careful clinical monitoring or by various technical monitoring methods. In head and neck surgery, where the flaps are often buried and difficult to monitor clinically, a reliable technical monitoring method would be useful. A broad range of different techniques are in use varying according to practical and personal preferences among clinics and surgeons. However, no evidence for any particular technique being superb has emerged. We review reports of some frequently used and modern free flap monitoring techniques. RECENT FINDINGS: Clinical monitoring is still the gold standard to which other techniques are compared to. Laser Doppler flowmetry and near-infrared spectroscopy have been reported to identify early circulatory problems, but both techniques are not well suited for buried flaps. Implantable Doppler, flow coupler, partial tissue oxygen pressure and microdialysis are invasive monitoring methods suitable for buried flaps. SUMMARY: More research with practical and clinically relevant parameters, that is flap salvage rate, false positive rate and cost-efficiency are needed before objective comparisons between different monitoring techniques can be made.

Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer.

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.