Distinct eicosanoid patterns in severe recalcitrant nasal polyposis.

BACKGROUND: Although altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent nasal polyps (NPs) is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence (NPR) and explored potential endotypes based on pre-surgical eicosanoid levels. METHODS: Levels of leukotriene (LT) E4 , LTB4 , prostaglandin (PG) D2 , PGE2 and 15(S) hydroxyeicosatetraenoic acid (15[S]-HETE) were measured in nasal secretions with specific immunoassays at pre-surgery (n = 38) and 6 and 12 months post-surgery (n = 35), with NPR identified endoscopically. Pre- and post-surgical levels were compared between patients with and without NPR. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters. RESULTS: Patients with recurrent NPs had pronounced pre-surgical levels of nasal 15(S)-HETE, PGD2 and LTE4 . From pre-surgery to 12 months post-surgery, NPR was associated with significant decreases of 15(S)-HETE and PGD2 relative to non-recurrence, whereas levels of LTE4 decreased at 6 months but increased again at 12 months. Clustering revealed three potential endotypes. Clusters 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2 , lower levels of PGE2 and LTB4 , and more cases of recurrent NPs and previous NP surgeries. CONCLUSION: Elevated nasal LTE4 12 months post-surgery in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies.

Levels of eicosanoids in nasal secretions associated with nasal polyp severity in chronic rhinosinusitis.

Severe nasal polyposis and mucosal inflammation, in patients with chronic rhinosinusitis (CRS) may include a dysregulated eicosanoid profile, but a clinical role for eicosanoids in CRS with nasal polyps (NP; CRSwNP) remains to be elucidated. This study focused on assessing levels and clinical implications of inflammatory mediators in nasal secretions and urine from patients with different NP severity or Aspirin Exacerbated Respiratory Disease (AERD). Levels of leukotrienes E4 and B4, prostaglandins D2 and E2 as well as 15(S)-hydroxyeicosatetraenoic acid were measured with enzyme immunoassays and cytokines with magnetic bead immunoassays. Patients with CRSwNP were subdivided based on NP score; CRSwNP-low (NP score ≤ 4, n = 11) or CRSwNP-high (NP score ≥ 5, n = 32) and compared to CRS without polyps (CRSsNP, n = 12), CRSwNP-AERD (n = 11) and individuals without CRS (n = 25). Smell test score, fractional exhaled nitric oxide (FeNO), blood eosinophils and Sinonasal outcome test-22 were assessed as clinical markers. Leukotriene E4, prostaglandin D2 and 15(S)-hydroxyeicosatetraenoic acid in nasal secretions correlated with NP score. Nasal leukotriene E4 also correlated with FeNO and smell test score, with highest levels found in CRSwNP-AERD. Levels of prostaglandin D2 in nasal secretion as well as urinary levels of the prostaglandin D2 metabolite 11ß-prostaglandin F2α differed between CRSNP-high and CRSwNP-low. Urinary 11ß-prostaglandin F2α was associated with asthma comorbidity whereas a similar association with prostaglandin D2 in nasal secretions was not observed. In conclusion, subdividing patients based on NP severity in combination with analysis of eicosanoids in non-invasively collected nasal secretions, may have clinical implications when assessing CRS disease severity.

Hot saline irrigation in comparison to nasal packing after sinus surgery.

OBJECTIVES: Previous studies have shown that hot saline solution (HSS) nasal irrigation is effective against nasal bleeding and is used to treat nasal hemorrhage. In a pilot study, we evaluated hot saline nasal irrigation in comparison to a routinely used nasal packing in terms of self-reported complications and mucosal healing after functional endoscopic sinus surgery. METHODS: Patients undergoing surgery for bilateral chronic rhinosinusitis received polyvinyl acetate (PVA) nasal packing in the left nostril, and the right nostril was rinsed with 47°C sterile saline immediately after surgery. Patients' experiences of pain, bleeding, and other types of uncomfortable experiences were measured using a visual analog scale for each nostril before, during, and immediately after nasal packing removal. Two weeks post-surgery, the assessments were repeated including an endoscopic evaluation of the mucosa by the surgeon. RESULTS: Twenty-seven patients completed the study. Prior to removal of the packing, the patients experienced significantly more pain and other uncomfortable experiences in the nostril treated with nasal packing, as compared to the nostril solely rinsed with hot saline. After removal, patients reported significantly more uncomfortable experiences from the packing treated nostril. Two weeks post-surgery, no difference in mucosal healing was observed between the two nostrils. CONCLUSIONS: The results from this study indicate that irrigation with HSS could be an alternative postoperative treatment to conventional PVA nasal packing. Hot saline irrigation may contribute to patients experiencing improved control of postoperative bleeding, pain, and less suffering of other causes as well as health-economic benefits, without affecting the mucosal healing up to 2 weeks post-surgery. LEVEL OF EVIDENCE: 1b.

New Algorithm for the Management of Orbital Blowout Fracture Based on Prospective Study.

Despite extensive debate and publications in the management of blowout fracture (BOF), there are still considerable differences in the surgeons' management of BOF due to a lack of reliable evidence-based studies. This article aimed to evaluate which BOF patients require surgical treatment due to functional and/or cosmetic deformities; evaluate which computed tomography (CT) scan findings predict these problems; and provide an algorithm in the management of BOF. Seventy-nine patients with BOF were treated conservatively and followed up prospectively regarding functional and cosmetic deformities for at least 1 year. The patients' CT scans were analyzed and several measurements were performed. Patients' symptoms and the clinical findings were correlated to the CT scan measurements. We found visible deformity in 37% of the patients, but only 10% chose to proceed to surgery due to cosmetic deformities. In patients with inferior BOF and a herniation < 1.0 mL, a visible deformity was found when the ratio between fracture and the fractured orbital wall areas was ≥42%, or the total area of the fracture was ≥ 2.3 cm 2 . In patients with inferior BOF and a herniation ≥ 1.0 mL, a visible deformity was found when the distance from the inferior orbital rim to the posterior edge of the fracture was ≥ 3.0 cm. In patients with inferomedial fracture, a visible deformity was found when the herniation was ≥ 0.9 mL. Diplopia improved significantly and remained in only 3% of the patients in nonoperated group. Hypoesthesia of the infraorbital nerve improved significantly, but 23% of the nonoperated and 50% of the operated patients still experienced loss of sensation at final control. In this prospective study, we found that not only herniated orbital volume but also other CT scan findings in BOF were crucial to predict late visible deformities. Based on these findings, we propose an algorithm for the prediction of late visible deformity with 83% accuracy. There are indications that diplopia without ocular motility disorder is due to edema and we recommend observation as long as the diplopia improves gradually.

Prospective Randomized Controlled Pilot Study on Orbital Blowout Fracture.

To clarify the conflicting recommendations for care of blowout fracture (BOF), a prospective randomized study is required. Here, we present a prospective randomized pilot study on BOF. This article aimed to evaluate which computed tomography (CT) findings predict late functional and/or cosmetic symptoms in BOF patients with ≥ 1.0 mL herniation of orbital content into maxillary and/or ethmoidal sinuses. It also aimed to evaluate which patients with BOF would benefit from surgical treatment or observational follow-up. Twenty-six patients with BOF ≥ 1.0 mL herniation were randomized to observational ( n = 10) or surgical treatments ( n = 16) and were followed up for functional and cosmetic symptoms for at least 1 year. The results from CT scan measurements were correlated to the patients' symptoms and clinical findings which we report in this pilot study. Of the 10 patients randomized to observation, five had an inferomedial BOF with a herniation of ≥ 1.3 mL and all patients developed cosmetic deformities and required surgery. The remaining five patients in the observational group had inferior BOF and one of them had a distance of 3.3 cm from the inferior orbital rim to the posterior edge of the fracture and developed a cosmetic deformity but was unwilling to proceed to surgical treatment, and four patients had a median distance of 2.9 cm from the inferior orbital rim to the posterior edge of the fracture and did not develop cosmetic deformities. The median time from injury to surgery was 13 (3-17) days for the surgical group and 37 (17-170) days for the patients who underwent surgery in the observational group. The surgical results were similar for all the operated patients at the final control. Diplopia decreased and remained partly in one patient in the surgical group and in two patients in the observational group. Hypoesthesia of the infraorbital nerve decreased in nonsurgically treated patients, but surgery seemed to induce hypoesthesia. In this prospective randomized controlled pilot study on BOF, all patients in the observational group with inferomedial fractures developed visible deformity. Diplopia in BOF, without ocular motility limitation, is believed to be due to edema. Diplopia is not an indication for surgery as long as it reduces over time.

Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis.

Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n = 15; Stage II, n = 30; Stage III, n = 7; Stage IV, n = 13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress.

Still no reliable consensus in management of blow-out fracture.

BACKGROUND: Management of blow-out fractures (BOF) is addressed by different specialties. The general agreement is that patients with the potential for late enophthalmus development require early surgical intervention. In this study we wanted to: (i) evaluate the differences in opinions between the specialties that manage BOF and also whether there was a difference between surgeons from different countries, (ii) evaluate if surgeons handle these cases based upon their own individual criteria,(1) (iii) evaluate the correlation between the management of patients with orbital floor fractures and any late sequelae detected upon eye examination. MATERIALS AND METHODS: Eleven patients with BOF were selected from the records of the Department of ENT and Head & Neck Surgery, Karolinska University Hospital between 2003 and 2008. The cases were presented with a case history and CT scans to 46 surgeons from different countries and specialties and they were asked to give their opinions regarding the need for surgery, timing of surgery and the risk for late enophthalmus. We considered a group of surgeons to be in agreement if there was ≥ 75% agreement on whether or not to operate, when to operate and on the risk for late enophthalmus. RESULT: The surgeons agreed on the choice of management for the patients (whether or not to operate) in only 5 of the 11 cases. Similarly, in only 5 of the 11 cases did the surgeons agree upon the risk for late enophthalmus. There was a greater difference between specialities than between physicians from the participating countries. CONCLUSION: There are considerable differences in opinions regarding the management of BOF due to a lack of a reliable consensus. The management of BOF appears to be based on both individual and local traditions. Guidelines based on a randomized prospective study in BOF are required.

Cyclooxygenase-2 expression in oral tongue squamous cell carcinoma.

BACKGROUND: Cyclooxygenase-2 expression is associated with unfavorable outcome in various cancers, and evidence is accumulating that carcinogenesis possibly evolves from intracellular changes in response to induction of this enzyme. Today selective cyclooxygenase-2 inhibitors are being studied and used as complement in cancer treatment. This study examined the prognostic value of cyclooxygenase-2 expression in oral tongue squamous cell carcinoma (OTSCC). METHODS: Expression of cyclooxygenase-2 was determined in biopsies from 76 stage matched patients with OTSCC by immunohistochemistry between January 2000 and December 2004 in Stockholm, Sweden. Additionally, twelve samples taken after pre-operative radiotherapy were investigated. RESULTS: All OTSCC specimen expressed cyclooxygenase-2 by immunostaining. The cyclooxygenase-2 staining intensity increased significantly with more advanced stage (P=0.020). Fifty percent of the surgical specimen showed a decrease in immunostaining post-radiation (P=0.031). No association was found with survival. CONCLUSION: Cyclooxygenase-2 expression has limited prognostic value in OTSCC.

EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma.

New promising therapeutic agents targeting epidermal growth factor receptor (EGFR) have been developed although clinical information concerning EGFR status in oral tongue squamous cell carcinoma (OTSCC) is limited. We investigated EGFR protein expression and gene copy numbers in 78 pretreatment OTSCC paraffin samples. EGFR protein expression was found in all 78 tumours, of which 72% showed an intense staining. Fifty-four percent of the tumours had high (> or =four gene copies) EGFR gene copy numbers. EGFR gene copy number was significantly associated with EGFR protein expression (P=0.002). Pretreatment EGFR staining intensity tended to be associated with non-pathological complete remission after preoperative radiotherapy for Stage II OTSCC. No correlation was found between EGFR status and survival. EGFR FISH results were significantly (P=0.003) higher in more advanced tumours (Stages II, III and IV) than in the tumours in Stage I. Non-smokers exhibited a significantly higher EGFR gene copy number and protein overexpression in Stages I and II OTSCC than smokers (P=0.001, P=0.009). In conclusion, EGFR was found to be overexpressed in all OTSCCs making this cancer type interesting for exploring new therapeutic agents targeting the EGFR receptor.

The incidence of tonsillar cancer in Sweden is increasing.

CONCLUSIONS: The incidence of tonsillar cancer in Sweden is increasing, particularly among men. Risk factors other than smoking may have contributed to the observed secular trend in men. In women, however, smoking can be a part of the explanation. Further studies to look at changes in other environmental factors, such as human papilloma virus (HPV) infection, are clearly warranted. OBJECTIVES: Head and neck cancer is related to smoking habits and smoking has decreased substantially during the last 30 years in Sweden. However, there is suspicion that the incidence of tonsillar cancer has increased in the last 30 years as it has in the USA and Finland, in spite of reduced prevalence of known risk factors. The time trends of oral and oropharygeal cancer have been studied in Sweden, but not tonsillar cancer specifically. SUBJECTS AND METHODS: We used the Swedish Cancer Registry to assess the secular trend of incidence of tonsillar cancer in Sweden since 1960. For comparison we investigated the incidence of other oral cancers and lung cancer, which are also smoking-related. The prevalence of smoking was investigated for reference. Age-standardized incidence rates were calculated and linear regression was used to evaluate secular trends. RESULTS: The incidence of tonsillar cancer increased by 2.6% per year in men and 1.1% in women. No similar increase was seen in the other oral cancers. For lung cancer there was a decrease in the incidence in men, but in women the incidence is still increasing.