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.

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.

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.

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.

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.

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.

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.

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.

Improved outcomes with oral tongue squamous cell carcinoma in Finland.

BACKGROUND: Incidence rates for oral tongue squamous cell carcinoma (SCC) are steadily rising worldwide. METHODS: All patients diagnosed with primary oral tongue SCC at the 5 university hospitals in Finland from 2005 to 2009 were studied. The mean follow-up time was 43 months (median, 54 months; range, 0-111 months). RESULTS: Three hundred sixty patients with primary oral tongue SCC were identified. Treatment with curative intent was provided for 328 patients (91%). The 5-year disease-specific survival (DSS) rates were as follows: stage I 87%; stage II 73%; stage III 69%; and stage IV 51%. The 5-year recurrence-free survival in general has improved from 47% in our previous published series (1995-1999) to 65% in the current series (p < .001). CONCLUSION: The outcome of oral tongue SCC has significantly improved in Finland. However, the relatively high number of disease recurrences in patients with stage I and II disease, when compared with patients with stage III and IV disease, calls for an investigation of new treatment approaches. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1306-1312, 2017.

Next-Generation Sequencing Combined with Specific PCR Assays To Determine the Bacterial 16S rRNA Gene Profiles of Middle Ear Fluid Collected from Children with Acute Otitis Media.

The aim of the study was to analyze the bacteriome of acute otitis media with a novel modification of next-generation sequencing techniques. Outpatient children with acute otitis media were enrolled in the study, and middle ear fluids were collected during 90 episodes from 79 subjects aged 5 to 42 months (median age, 19 months). The bacteriome profiles of middle ear fluid samples were determined by a nested-PCR amplification of the 16S rRNA gene (V4 region), followed by mass sequencing. The profiling results were compared to the results of specific PCR assays targeting selected prevalent pathogens. Bacteriome profiling using nested amplification of low-volume samples was aided by a bioinformatic subtraction of signal contaminants from the recombinant polymerase, achieving a sensitivity slightly lower than that of specific PCR detection. Streptococcus pneumoniae was detected in 28 (31%) samples, Haemophilus influenzae in 24 (27%), Moraxella catarrhalis in 18 (20%), Staphylococcus spp. in 21 (23%), Turicella otitidis in 5 (5.6%), Alloiococcus otitidis in 3 (3.3%), and other bacteria in 14 (16%) using bacteriome profiling. S. pneumoniae was the dominant pathogen in 14 (16%) samples, H. influenzae in 15 (17%), M. catarrhalis in 5 (5.6%), T. otitidis in 2, and Staphylococcus auricularis in 2. Weaker signals of Prevotella melaninogenica, Veillonella dispar, and Veillonella montpellierensis were noted in several samples. Fourteen samples (16%) were not explainable by bacterial pathogens; novel causative agents were not detected. In conclusion, unbiased bacteriome profiling helped in depicting the true mutual quantitative ratios of ear bacteria, but at present, its complicated protocol impedes its routine clinical use. IMPORTANCE Although S. pneumoniae, H. influenzae, and M. catarrhalis have been long established as the most important pathogens in acute otitis media using culture and specific PCR assays, the knowledge of their mutual quantitative relations and possible roles of other bacteria is incomplete. The advent of unbiased bacteriome 16S rRNA gene profiling has allowed the detection of nearly all bacteria present in the sample, and it helps in depicting their mutual quantitative ratios. Due to the difficulties in performing mass sequencing in low-volume samples, only a few bacteriome-profiling studies of otitis media have been published, all limited to cases of chronic otitis media. Here, we present a study on samples obtained from young children with acute otitis media, successfully using a strategy of nested PCR coupled with mass sequencing, and demonstrate that the method can confer quantitative information hardly obtainable by other methods.

The feasibility of NBI in patients with suspected upper airway lesions: A multicenter study.

OBJECTIVE: Narrow band imaging (NBI) improves diagnosis of laryngopharyngeal cancer, but most reported NBI studies are from experienced centers. Feasibility reports on use at everyday outpatient departments are needed. STUDY DESIGN: Researcher-initiated, prospective, multicenter. METHODS: Participating physicians were instructed in NBI technique during a 4-hour meeting. Patients underwent an examination that included endoscopy with white light (WL) high-definition (HD) TV and NBI filter in the selected time period. All suspicious lesions were biopsied. The medical records of patients with NBI negative findings were evaluated 6 months after the visit to detect all possible malignant lesions coming into view at mucosal sites. These were considered as false-negative cases, enabling long-term assess to the positive predictive value (NPV) of the protocol. RESULTS: We enrolled 125 patients. Of those, 84 (67.2%) were males and the median age was 65 years (range, 35-91). In analysis of the accuracy of WL HD TV and NBI against biopsy, the sensitivity and specificity of WL HD TV were 62% and 81%, respectively; and the sensitivity and specificity of NBI were 100% and 84%, respectively. The diagnostic accuracy of NBI was significantly better (P < 0.05). When analyzing medical records 6 months after the initial examination, we found three patients who had been diagnosed with a malignant lesion (NPV of NBI of 96.8%). CONCLUSION: Narrow band imaging is readily implemented in an everyday outpatient practice, and there seems to be better detection rates of dysplastic/carcinoma lesions with HD NBI compared to HD WL. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:1821-1825, 2017.

Human enterovirus and rhinovirus infections are associated with otitis media in a prospective birth cohort study.

BACKGROUND: Human enteroviruses (HEVs) and rhinoviruses (HRVs) have been linked to acute otitis media (AOM). OBJECTIVES: The present study evaluates the aforementioned association in a birth cohort setting. STUDY DESIGN: The cohort included 286 healthy infants (191 boys) followed from birth up to the age of 2 years in the Type 1 Diabetes Prediction and Prevention study in Finland. Stool samples were collected monthly and analyzed for the presence of HRV and HEV RNA using RT-PCR. Clinical symptoms were recorded by a questionnaire every 3-6 months. RESULTS: Altogether 610 AOM episodes were reported during the follow-up. 9.8% of the stool samples were positive for HRV and 6.8% for HEV. HRV positivity peaked at the age of 3-6 months declining gradually after this age, whereas HEV positivity peaked later, at the age of 12-24 months. The risk of AOM was increased in children who were HEV positive at least once at the age of 6-12 months (OR 2.2 [95%CI 1.1-4.2], P=0.023) or who were HRV positive at least once at the age of 18-24 months (OR 2.3 [95%CI 1.0-5.2], P=0.042). Having an older sibling, short breast-feeding and maternal smoking during pregnancy were also significantly associated with AOM. CONCLUSIONS: HRV and HEV infections are frequent during the first months of life. The observed trend for increased risk of AOM in HRV and HEV positive children is in line with the results from hospital series suggesting that these viruses may play an independent role in the pathogenesis of AOM.

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.

Antibiotic resistance in pathogens causing acute otitis media in Finnish children.

INTRODUCTION: Microbiology and susceptibility of middle ear pathogens in children change over time and antibiotic resistance is increasing globally. For the clinicians it is important to be up to date about the resistance situation when considering antibiotic treatment in acute otitis media (AOM). In this study we analysed the resistance profile of AOM pathogens in out-patient children in Finland. METHODS AND MATERIALS: A total of 41 culture positive middle ear fluid (MEF) samples were analysed for bacteria and the presence of antibiotic resistant strains. The samples were obtained from children aged six - 39 months who participated in the otitis media trial during one year period. RESULTS: The most common pathogen was Haemophilus influenzae 17 (40%), followed by Streptococcus pneumoniae in 15 (35%) and Moraxella catarrhalis in 8 (19%). Other pathogens were detected in 3 (7%) of cases. Antibiotic resistance or diminished sensitivity was seen in 63% of the detected bacteria and 28% of pathogens produced beta-lactamase. CONCLUSIONS: Antibiotic resistant bacterial strains causing AOM have increased in Finland. Nevertheless, most of the pathogens (72%) were sensitive to amoxicillin, which is still recommended as the first line antibiotic in the treatment of AOM.

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.

The Effect of Norepinephrine and Dopamine on Radial Forearm Flap Partial Tissue Oxygen Pressure and Microdialysate Metabolite Measurements: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing ablative and reconstructive head and neck surgery with a microvascular flap have multiple factors that potentially decrease postoperative mean arterial pressure, which may endanger flap survival. The safety of vasopressor use has long been a topic of discussion. The authors analyzed the effect of vasopressors on microvascular flap perfusion after head and neck cancer reconstruction. METHODS: A total of 27 patients were enrolled in a randomized, controlled, clinical trial. A microvascular radial forearm flap was used for reconstruction. Patients were allocated into one of three groups: dopamine, norepinephrine, and control. The intervention groups received the vasoactive drug, aiming to maintain the mean arterial pressure between 80 and 90 mmHg. Normovolemia was maintained according to central venous pressure. Flap perfusion was monitored with continuous tissue partial pressure of oxygen and microdialysate metabolite (lactate-to-pyruvate ratio) measurements. RESULTS: No adverse effects were observed, and postoperative recovery was free of complications in all groups. Neither the lactate-to-pyruvate ratio nor continuous tissue partial pressure of oxygen values differed significantly between groups during the first 24 hours of the vasoactive drug infusion period or during the 72-hour follow-up. CONCLUSIONS: Norepinephrine and dopamine are safe and effective vasopressors for use during the postoperative period following head and neck cancer surgery with microvascular reconstruction. Dopamine should be used with caution, however, because of the risk of side effects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The expression and prognostic relevance of indoleamine 2,3-dioxygenase in tongue squamous cell carcinoma.

Conclusion IDO might be useful for predicting progression of primary tumor stage T2 and T3 in tongue squamous cell carcinoma (TSCC), but does not seem like a specific biomarker for diagnosing TSCC and predicting patient survival. Objectives Indoleamine 2,3-dioxygenase (IDO) is expressed in many cells and it catabolises the essential amino acid tryptophan to kynurenine. IDO acts as an immune modulator through suppression of T-cell immunity and other pathways. In cancer cells, IDO has been proposed to promote tumor progression by enabling malignant cells to escape from the immune system. The aim of this study was to evaluate the association and prognostic relevance of IDO expression in TSCC. Method One hundred and eight retrospective tongue and lymph node specimens were stained immunohistochemically with monoclonal antibody anti-indoleamine 2,3-dioxygenase. The relative abundance of IDO positive epithelial cells, IDO staining intensity, and inflammation were assessed semi-quantitatively with light microscopy. Results IDO was expressed stronger in tongue hyperplasia than in TSCC. However, IDO expression associated with poor survival in the sub-groups with primary tumor stage T2-T4 and in the sub-group with strong inflammation in tumors' invasive front.

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.

Laryngeal cancer in Finland: A 5-year follow-up study of 366 patients.

BACKGROUND: The purpose of this study was to acquire nationwide data on the management and outcome of laryngeal squamous cell carcinoma (SCC) in Finnish university hospitals over a 5-year posttreatment follow-up. METHODS: All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed. RESULTS: Three hundred sixty-six patients with laryngeal cancer were identified, 360 of whom had laryngeal SCC. Three hundred forty-two patients with laryngeal SCC (95%) were treated with curative intent. Five-year disease-specific survival (DSS) for T1a, T1b, T2, T3, and T4 glottic SCC was 100%, 95%, 78%, 79%, and 53%, respectively. The corresponding figures for T1 to T4 supraglottic SCC were 68%, 54%, 72%, and 59%. CONCLUSION: Results of this nationwide study give a general overview of the outcome of unselected patients treated with unified guidelines. Patients with T2 tumors, usually treated with radiotherapy (RT), had a worse prognosis than expected. This patient group warrants further investigation and possibly treatment intensification.