The dysadherin/FAK axis promotes individual cell migration in colon cancer.

Dysregulation of cancer cell motility is a key driver of invasion and metastasis. High dysadherin expression in cancer cells is correlated with invasion and metastasis. Here, we found the molecular mechanism by which dysadherin regulates the migration and invasion of colon cancer (CC). Comprehensive analysis using single-cell RNA sequencing data from CC patients revealed that high dysadherin expression in cells is linked to cell migration-related gene signatures. We confirmed that the deletion of dysadherin in tumor cells hindered local invasion and distant migration using in vivo tumor models. In this context, by performing cell morphological analysis, we found that aberrant cell migration resulted from impaired actin dynamics, focal adhesion turnover and protrusive structure formation upon dysadherin expression. Mechanistically, the activation of focal adhesion kinase (FAK) was observed in dysadherin-enriched cells. The dysadherin/FAK axis enhanced cell migration and invasion by activating the FAK downstream cascade, which includes the Rho family of small GTPases. Overall, this study illuminates the role of dysadherin in modulating cancer cell migration by forcing actin dynamics and protrusive structure formation via FAK signaling, indicating that targeting dysadherin may be a potential therapeutic strategy for CC patients.

SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment.

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.

Machine learning with in silico analysis markedly improves survival prediction modeling in colon cancer patients.

BACKGROUND: Predicting the survival of cancer patients provides prognostic information and therapeutic guidance. However, improved prediction models are needed for use in diagnosis and treatment. OBJECTIVE: This study aimed to identify genomic prognostic biomarkers related to colon cancer (CC) based on computational data and to develop survival prediction models. METHODS: We performed machine-learning (ML) analysis to screen pathogenic survival-related driver genes related to patient prognosis by integrating copy number variation and gene expression data. Moreover, in silico system analysis was performed to clinically assess data from ML analysis, and we identified RABGAP1L, MYH9, and DRD4 as candidate genes. These three genes and tumor stages were used to generate survival prediction models. Moreover, the genes were validated by experimental and clinical analyses, and the theranostic application of the survival prediction models was assessed. RESULTS: RABGAP1L, MYH9, and DRD4 were identified as survival-related candidate genes by ML and in silico system analysis. The survival prediction model using the expression of the three genes showed higher predictive performance when applied to predict the prognosis of CC patients. A series of functional analyses revealed that each knockdown of three genes reduced the protumor activity of CC cells. In particular, validation with an independent cohort of CC patients confirmed that the coexpression of MYH9 and DRD4 gene expression reflected poorer clinical outcomes in terms of overall survival and disease-free survival. CONCLUSIONS: Our survival prediction approach will contribute to providing information on patients and developing a therapeutic strategy for CC patients.

DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.

Rationale: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that selectively marks cancer stem-like cells (CSCs) and promotes malignant progression in colorectal cancer (CRC). However, the exact molecular mechanism by which DCLK1 drives the aggressive phenotype of cancer cells is incompletely determined. Methods: Here, we performed comprehensive genomics and proteomics analyses to identify binding proteins of DCLK1 and discovered X-ray repair cross-complementing 5 (XRCC5). Thus, we explored the biological role and downstream events of the DCLK1/XRCC5 axis in human CRC cells and CRC mouse models. Results: The results of comprehensive bioinformatics analyses suggested that DCLK1-driven CRC aggressiveness is linked to inflammation. Mechanistically, DCLK1 bound and phosphorylated XRCC5, which in turn transcriptionally activated cyclooxygenase-2 expression and enhanced prostaglandin E2 production; these events collectively generated the inflammatory tumor microenvironment and enhanced the aggressive behavior of CRC cells. Consistent with the discovered mechanism, inhibition of DCLK1 kinase activity strongly impaired the tumor seeding and growth capabilities in CRC mouse models. Conclusion: Our study illuminates a novel mechanism that mediates the pro-inflammatory function of CSCs in driving the aggressive phenotype of CRC, broadening the biological function of DCLK1 in CRC.

Dysadherin awakens mechanical forces and promotes colorectal cancer progression.

Rationale: Dysadherin is a tumor-associated, membrane-embedded antigen found in multiple types of cancer cells, and associated with malignant behavior of cancer cells; however, the fundamental molecular mechanism by which dysadherin drives aggressive phenotypes of cancer is not yet fully determined. Methods: To get a mechanistic insight, we explored the physiological relevance of dysadherin on intestinal tumorigenesis using dysadherin knockout mice and investigated its impact on clinicopathological features in patients with advanced colorectal cancer (CRC). Next, to discover the downstream signaling pathways of dysadherin, we applied bioinformatic analysis using gene expression data of CRC patient tumors and dysadherin knockout cancer cells. Additionally, comprehensive proteomic and molecular analyses were performed to identify dysadherin-interacting proteins and their functions. Results: Dysadherin deficiency suppressed intestinal tumorigenesis in both genetic and chemical mouse models. Moreover, increased dysadherin expression in cancer cells accounted for shorter survival in CRC patients. Comprehensive bioinformatics analyses suggested that the effect of dysadherin deletion is linked to a reduction in the extracellular matrix receptor signaling pathway. Mechanistically, the extracellular domain of dysadherin bound fibronectin and enhanced cancer cell adhesion to fibronectin, facilitating the activation of integrin-mediated mechanotransduction and leading to yes-associated protein 1 activation. Dysadherin-fibronectin interaction promoted cancer cell growth, survival, migration, and invasion, effects collectively mediated the protumor activity of dysadherin. Conclusion: Our results highlight a novel function of dysadherin as a driver of mechanotransduction that stimulates CRC progression, providing a potential therapy strategy for CRC.

The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression.

Recurrence and metastasis remain major obstacles in colorectal cancer (CRC) treatment. Recent studies suggest that a small subpopulation of cells with a self-renewal ability, called cancer stem-like cells (CSCs), promotes recurrence and metastasis in CRC. Unfortunately, no CSC inhibitor has been demonstrated to be more effective than existing chemotherapeutic drugs, resulting in a significant unmet need for effective CRC therapies. In this study, transcriptomic profiling of metastatic tumors from CRC patients revealed significant upregulation in the Wnt pathway and stemness genes. Thus, we examined the therapeutic effect of the small-molecule Wnt inhibitor ICG-001 on cancer stemness and metastasis. The ICG-001 treatment efficiently attenuated self-renewal activity and metastatic potential. Mechanistically, myeloid ecotropic viral insertion site 1 (MEIS1) was identified as a target gene of ICG-001 that is transcriptionally regulated by Wnt signaling. A series of functional analyses revealed that MEIS1 enhanced the CSC behavior and metastatic potential of the CRC cells. Collectively, our findings suggest that ICG-001 efficiently inhibits CRC stemness and metastasis by suppressing MEIS1 expression. These results provide a basis for the further clinical investigation of ICG-001 as a targeted therapy for CSCs, opening a new avenue for the development of novel Wnt inhibitors for the treatment of CRC metastasis.

Correlation of Nasal Eosinophilia and Response after Nasal Provocation Test in Patients with Nonallergic Rhinitis.

Objectives We aimed to evaluate the relationship between nasal eosinophilia and nasal hyperresponsiveness to allergen extract. Study Design Retrospective chart review. Setting Academic tertiary rhinologic practice. Subjects and Methods We performed allergy tests (skin prick test and multiple allergosorbent test) and nasal cytology for 194 patients with rhinitis symptoms (76 males and 118 females; age, 11-69 years). According to the results, they were classified into 4 groups: group A (allergic rhinitis with eosinophilia, n = 26), group B (allergic rhinitis without eosinophilia, n = 77), group C (nonallergic rhinitis with eosinophilia syndrome, n = 20), and group D (nonallergic rhinitis without eosinophilia, n = 71). We performed a nasal provocation test (NPT) using house dust mite extract and assessed the changes in symptoms and the decrease in acoustic parameters (total nasal volume and minimal cross-sectional area [MCA]). Results Patients in group C were more likely to have severe rhinorrhea and sneezing than those in group D ( P < .001). After NPT, group C had greater aggravation of nasal obstruction than group D ( P < .001). Group C also showed markedly greater MCA changes as compared with group D 15 minutes after the antigen challenge ( P = .002). There was significant correlation between the number of eosinophils and an increase in nasal obstruction ( r = 0.319, P = .0009), rhinorrhea ( r = 0.302, P = .0017), sneezing ( r = 0.219, P = .0241), change in the total nasal volume 15 minutes after NPT ( r = 0.287, P = .0028), and change in the MCA 15 minutes ( r = 0.322, P = .0008) and 30 minutes ( r = 0.250, P = .0098) after NPT. Conclusion In patients with NAR, nasal eosinophilia is associated with provocative response after NPT. Further research should be performed to elucidate the mechanisms that underlie this phenomenon.

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis.

We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1ß was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury.

OBJECTIVES: Antiorthostatic suspension (AOS) is ground-based model of simulated microgravity. There is still no study about the effect of long-term microgravity on the clinical course of acute lung injury. We evaluated the effect of simulated microgravity using AOS in a murine model of acute lung injury by lipopolysaccharide (LPS). METHODS: Thirty BALB/c mice were used. During 4 weeks, mice were equally allocated to control (free movement), restraint (tail suspended, but hindlimbs not unloaded), and AOS group (hindlimb unloaded). After then, mice got intranasal challenge with LPS (20 mg/kg, 50 µL). We measured: weight gain before and after AOS, the number of inflammatory cells and titers of cytokines (interleukin [IL]-1ß, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) in bronchoalveolar lavage (BAL) fluid, titer of myeloperoxidase (MPO) in serum and lung homogenate, and histopathologic examination of lung tissue. RESULTS: AOS group had significant weight loss compared to control and restraint group (P<0.001). AOS group also showed significantly decreased lymphocytes (P=0.023) compared to control group. In AOS group, titer for IL-1ß in BAL fluid was significantly lower than restraint group (P=0.049). Titer for serum MPO was significantly decreased in AOS group compared to restraint group (P=0.004). However, there was no significant difference of MPO titers in lung tissue between groups. Histopathologic examination of lung tissue revealed no significant difference in the degree of pulmonary infiltration between restraint and AOS group. CONCLUSION: In spite of modest anti-inflammatory effect, prolonged AOS caused no significant change in LPS-induced pulmonary inflammation.

Hypergravity Effects on the Retina and Intraocular Pressure in Mice.

BACKGROUND: We investigated the effect of exposure to +10.0 G for 4 h on the intraocular pressure and the retina of mice. METHODS: We exposed 10 mice to +10.0 Gz for 4 h by using a centrifugal acceleration test facility for animals. Intraocular changes were compared before and after hypergravity exposure. The eyeballs of the mice were enucleated after measuring the intraocular pressure. Tissue slides of the retina were prepared with hematoxylin and eosin (H&E) for histological examination and immunohistochemical analyses for vascular endothelial growth factor-A (VEGF-A), VEGF receptor 1 (VEGF-R1), VEGF-R2, glial fibrillary acidic protein (GFAP), and glutamine synthetase (GS). RESULTS: The average intraocular pressure was 7.7 ± 0.86 mmHg before the hypergravity exposure and 6.65 ± 0.67 mmHg after the exposure. No histological difference was observed between the retinas in the two groups. The levels of VEGF-A, VEGF-R1, VEGF-R2, GFAP, and GS as assessed by immunohistochemistry were increased in the group exposed to hypergravity compared to the control group. DISCUSSION: Repeated exposure to a high level of hypergravity could cause elevation of intraocular pressure and hypoxic damage to the retina.

Interleukin-33 and Mast Cells Bridge Innate and Adaptive Immunity: From the Allergologist's Perspective.

Interleukin (IL) 33, a member of the IL-1 superfamily, is an "alarmin" protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcεRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis.

Computed tomography and magnetic resonance imaging findings of nasal cavity hemangiomas according to histological type.

OBJECTIVE: To compare computed tomography (CT) and magnetic resonance imaging (MRI) findings between two histological types of nasal hemangiomas (cavernous hemangioma and capillary or lobular capillary hemangioma). MATERIALS AND METHODS: CT (n = 20; six pre-contrast; 20 post-enhancement) and MRI (n = 7) images from 23 patients (16 men and seven women; mean age, 43 years; range, 13-73 years) with a pathologically diagnosed nasal cavity hemangioma (17 capillary and lobular capillary hemangiomas and six cavernous hemangiomas) were reviewed, focusing on lesion location, size, origin, contour, enhancement pattern, attenuation or signal intensity (SI), and bony changes. RESULTS: The 17 capillary and lobular hemangiomas averaged 13 mm (range, 4-37 mm) in size, and most (n = 13) were round. Fourteen capillary hemangiomas had marked or moderate early phase enhancement on CT, which dissipated during the delayed phase. Four capillary hemangiomas on MRI showed marked enhancement. Bony changes were usually not seen on CT or MRI (seen on five cases, 29.4%). Half of the lesions (2/4) had low SI on T1-weighted MRI images and heterogeneously high SI with signal voids on T2-weighted images. The six cavernous hemangiomas were larger than the capillary type (mean, 20.5 mm; range, 10-39 mm) and most had lobulating contours (n = 4), with characteristic enhancement patterns (three centripetal and three multifocal nodular), bony remodeling (n = 4, 66.7%), and mild to moderate heterogeneous enhancement during the early and delayed phases. CONCLUSION: CT and MRI findings are different between the two histological types of nasal hemangiomas, particularly in the enhancement pattern and size, which can assist in preoperative diagnosis and planning of surgical tumor excision.

Benzaldehyde suppresses murine allergic asthma and rhinitis.

To evaluate the antiallergic effects of oral benzaldehyde in a murine model of allergic asthma and rhinitis, we divided 20 female BALB/c mice aged 8-10 weeks into nonallergic (intraperitoneally sensitized and intranasally challenged to normal saline), allergic (intraperitoneally sensitized and intranasally challenged to ovalbumin), and 200- and 400-mg/kg benzaldehyde (allergic but treated) groups. The number of nose-scratching events in 10 min, levels of total and ovalbumin-specific IgE in serum, differential counts of inflammatory cells in bronchoalveolar lavage (BAL) fluid, titers of Th2 cytokines (IL-4, IL-5, IL-13) in BAL fluid, histopathologic findings of lung and nasal tissues, and expressions of proteins involved in apoptosis (Bcl-2, Bax, caspase-3), inflammation (COX-2), antioxidation (extracellular SOD, HO-1), and hypoxia (HIF-1α, VEGF) in lung tissue were evaluated. The treated mice had significantly fewer nose-scratching events, less inflammatory cell infiltration in lung and nasal tissues, and lower HIF-1α and VEGF expressions in lung tissue than the allergic group. The number of eosinophils and neutrophils and Th2 cytokine titers in BAL fluid significantly decreased after the treatment (P<0.05). These results imply that oral benzaldehyde exerts antiallergic effects in murine allergic asthma and rhinitis, possibly through inhibition of HIF-1α and VEGF.

Porous high-density polyethylene in functional rhinoplasty: Excellent long-term aesthetic results and safety.

BACKGROUND: Experience with the use of porous high-density polyethylene (PHDPE) for reconstruction of the nasal framework has been limited. OBJECTIVE: To confirm the safety and utility of PHDPE by analyzing aesthetic outcomes and assessing the frequency of complication related to PHDPE in a large, population-based, long-term follow-up study. METHODS: A total of 151 patients who had undergone septoplasty and/or functional rhinoplasty using PHDPE were enrolled. PHDPE sheets were used for diverse purposes such as septal extension graft, spreader graft, columellar strut or dorsal augmentation graft. After a long-term follow-up period (mean [± SD] 39.5±27.8 months; range six to 101 months), postoperative aesthetic outcome was evaluated objectively (by independent surgeons) and subjectively (patient self-report). Complications related to PHDPE were estimated through review of medical records. RESULTS: The most common use of the PHDPE graft was for septal extension (n=80 [42.6%]) and spreader graft (n=58 [30.9%]). Results of aesthetic evaluation by surgeons were excellent in 61 cases (40.4%), good in 54 (35.8%) and fair in 34 (22.5%). According to patient self-report, 100 were 'satisfied' (66.2%) and 36 rated their new profile as 'better than the preoperative profile' (23.8%). Complications were reported in six cases (4.0% [five cases of extrusion and one case of infection]). All complications were resolved after the surgical removal of PHDPE sheets under local anesthesia. CONCLUSION: The present study demonstrated that PHDPE could be used in functional primary rhinoplasty with excellent long-term aesthetic results and safety.

HISTORIQUE: L'expérience relative à l'utilisation de polyéthylène poreux de haute densité (PÉPHD) pour la reconstruction de la structure nasale est limitée. OBJECTIF: Confirmer l'innocuité et l'utilité du PÉPHD par l'analyse des résultats esthétiques et l'évaluation de la fréquence des complications qui y sont liées dans le cadre d'une vaste étude de suivi à long terme en population. MÉTHODOLOGIE: Au total, 151 patients qui avaient subi une septoplastie ou une rhinoplastie fonctionnelle au moyen de PÉPHD ont participé à l'étude. Les feuilles de PÉPHD ont été utilisées à plusieurs fins, telles qu'une greffe d'expansion de la cloison nasale, une greffe d'écartement, un étai columellaire ou une greffe d'augmentation dorsale. Après un suivi à long terme (moyenne [± ÉT] 39,5±27,8 mois; plage de six à 101 mois), les résultats esthétiques postopératoires ont été évalués de manière objective (par des chirurgiens indépendants) et subjective (par les patients mêmes). Les complications liées au PÉPHD ont été évaluées d'après l'examen des dossiers médicaux. RÉSULTATS: La greffe de PÉPHD était surtout utilisée pour l'expansion de la cloison nasale (n=80 [42,6 %]) et la greffe d'écartement (n=58 [30,9 %]). Les chirurgiens ont jugé les résultats esthétiques excellents dans 61 cas (40,4 %), bons dans 54 cas (35,8 %) et corrects dans 34 cas (22,5 %). Cent patients se sont dits « satisfaits ¼ (66,2 %) et 36 ont classé leur nouveau profil comme « meilleur que le profil préopératoire ¼ (23,8 %). Six cas ont présenté des complications (4,0 % [cinq cas d'extrusion et un cas d'infection]), qui se sont toutes résolues après l'extraction chirurgicale des feuilles de PÉPHD sous anesthésie locale. CONCLUSION: La présente étude a démontré que le PÉPHD pouvait s'associer à une innocuité et à des résultats esthétiques à long terme extrêmement satisfaisants dans le cadre d'une rhinoplastie primaire fonctionnelle.

Nonspecific hyper-reactivity and localized allergy: cause of discrepancy between skin prick and nasal provocation test.

OBJECTIVE: Disagreement between results of skin prick test (SPT) and nasal provocation tests (NPT) causes difficulty in differential diagnosis of allergic rhinitis (AR) and nonallergic rhinitis (NAR). We hypothesized this discrepancy could be due to the nonspecific hyper-reactivity (NHR) and localized allergy of the nasal cavity. STUDY DESIGN: Prospective pilot. SETTING: Academic tertiary rhinologic practice. SUBJECTS AND METHODS: Sixty patients with AR and 62 with NAR were enrolled. We categorized patients according to results of SPT and NPT. We compared: (1) the clinical characteristics and severity of the disease, (2) change of minimal cross-sectional area (MCA) and total nasal volume (TNV) after normal saline (NS) challenge, and (3) change of nasal symptoms and acoustic parameters after intranasal house dust mite (HDM) challenge between groups. RESULTS: Patients in groups A (SPT[+]/NPT[+]) and C (SPT[-]/NPT[+]) complained of more persistent discomfort than those in groups B (SPT[+]/NPT[-]) and D (SPT[-]/NPT[-]). The proportion of moderate to severe symptoms was significantly higher in groups A, B, and C compared to group D. After NS challenge, MCA/TNV showed a significantly greater decrease in groups A (MCA: 27.6% ± 21.3%, TNV: 24.6% ± 16.4%) and C (MCA: 31.2% ± 24.0%, TNV: 24.1% ± 23.4%) compared to groups B (MCA: 0.1% ± 13.2%, TNV: 3.9% ± 13.5%) and D (MCA: 2.1% ± 12.1%, TNV: 2.0% ± 17.2%) (P < .05). After HDM challenge, groups A/B showed a greater decrease in MCA (Group A: 62.4% ± 16.1%, Group B: 6.4% ± 11.3%) compared to groups C/D (Group C: 45.5% ± 14.4%, Group D: -3.0% ± 9.5%). CONCLUSION: NHR and/or localized allergy should be considered in patients with rhinitis whose SPT and NPT results are not in agreement.

Oncologic outcome after preoperative chemoradiotherapy in patients with pathologic T0 (ypT0) rectal cancer.

BACKGROUND: Little is known about the oncologic outcomes of patients with ypT0 rectal cancer after preoperative chemoradiotherapy. OBJECTIVE: To evaluate the clinicopathologic characteristics and oncologic outcomes of patients with ypT0 rectal cancer after preoperative chemoradiotherapy and curative radical surgery. DESIGN AND SETTINGS: This was a retrospective review of factors influencing outcome of patients treated with preoperative chemoradiotherapy for rectal cancer at a tertiary care university medical center in Seoul, Korea between 2000 and 2008. PATIENTS: A total of 830 rectal cancer patients underwent surgery after preoperative chemoradiotherapy. Patients were included in the study if they had a pretreatment clinical classification of T3-4 or N+ (or T2N0 and preoperative chemoradiotherapy for sphincter preservation) and if they were classified on pathologic examination as ypT0 after preoperative CRT and curative radical surgery. Patients were classified as. MAIN OUTCOME MEASURES: Overall survival and disease-free survival were evaluated in relation to ypT0N0 or ypT0N1-2 status and other factors that might influence outcome. RESULTS: Of 91 patients included in the study, 54 (59.3%) were men; the mean patient age was 55 (SD, 11) years, and mean follow-up duration was 44 (SD, 23) months. Surgical procedures included low anterior resection in 68 patients, abdominoperineal resection in 21, and intersphincteric resection in 2. Mean tumor distance from the anal verge was 4.7 (SD, 1.8) cm. Of the 91 patients, 85 were classified as ypT0N0 and 6 as ypT0N1-2. No patient experienced local recurrence. A total of 11 patients (12.1%) had distant metastases, after a mean 11.1 months, including 7 (8.2%) with ypT0N0 and 4 (66.7%) with ypT0N1-2 tumors. One patient with ypT0N0 and 2 patients with ypT0N1-2 tumors died of metastasis. In patients classified as ypT0N0, the 5-year disease free survival and overall survival rates were 82.3% and 89.2%, respectively. Multivariate analysis showed that ypN1-2 status (p = 0.001) was a significant independent risk factor for recurrence (decreased 5-year disease-free survival), but no factor was associated with 5-year overall survival. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSION: Oncologic outcomes in patients with ypT0N0 rectal cancer were excellent. The presence of residual cancer cells in mesorectal lymph nodes represents a risk factor for distant metastasis.

Feasibility of transanal minimally invasive surgery for mid-rectal lesions.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) has emerged as an alternative to transanal endoscopic microsurgery. We assessed the feasibility of TAMIS for lesions located in the mid rectum. METHODS: From July 2010 to October 2011, 16 consecutive patients with rectal pathology underwent TAMIS. After a single-incision laparoscopic surgery port was introduced into the anal canal, pneumorectum was established with a laparoscopic device, followed by transanal excision with conventional laparoscopic instruments, including graspers, monopolar electrocautery, and needle drivers. Clinicopathological findings, surgical procedure results, and perioperative outcomes were determined prospectively. RESULTS: Of the 16 patients, 11 had rectal cancers (3 T1 lesions and 8 after preoperative chemoradiotherapy), 4 had neuroendocrine tumors, and 1 had a mucocele. The median length of the lesions from anal verge was 7.5 cm (range 4-10 cm). All procedures were completed laparoscopically without conversion to conventional transanal approach. The median operating time was 86 min (range 33-160 min), and the median estimated blood loss was 15 ml (range 0-150 ml) with no patient requiring intraoperative transfusions. There was no surgical morbidity or mortality, but one patient died during follow-up due to synchronous advanced gastric cancer. The median postoperative hospital stay was 3 days (range 2-6 days). CONCLUSIONS: TAMIS seems to be a feasible and safe treatment option for lesions located in the mid rectum.

Immunologic properties and clinical features of local allergic rhinitis.

OBJECTIVE: There is still no study involving the immunologic properties of local allergic rhinitis (LAR). We aimed to determine the immunologic profile of patients with LAR by analyzing cytokines in the serum and nasal secretions and correlated the results with clinical characteristics. METHODS: Ten healthy volunteers (group A), nine patients with allergic rhinitis (group B), and seven patients with LAR (group C) were enrolled. MAIN OUTCOME MEASURES: Changes in nasal symptoms, total nasal volume (TNV), and minimal cross-sectional area (MCA) were compared. We performed a Quantibody array for interleukin (IL)-4, IL-13, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor, stem cell factor, IL-10, and transforming growth factor ß (TGF-ß) using serum and nasal secretions. RESULTS: Patients in group C had more aggravated rhinorrhea and itching than patients in group B (p < .05). The change in TNV and MCA was greater in groups B and C than in group A (p < .01). The serum concentration of IL-10 in group C was higher than in group A or B (p < .001). The concentration of IL-13, IL-5, IL-10, and TGF-ß in group C was higher than in group A or B in the nasal secretions (p < .001). CONCLUSIONS: Patients with LAR have similar symptoms, similar changes in TNV and MCA, and a similar profile of cytokine production and nasal secretions than those with allergic rhinitis. More prominent immunomodulating properties of LAR patients could in part explain the absence of systemic allergic responses.

Lymphoepithelial carcinoma of the nasal cavity mimicking juvenile angiofibroma.

Juvenile angiofibroma, nasopharyngeal carcinoma (NPC) and lymphoepithelial carcinoma of the nasal cavity (LEC NC) all could be found as a hyper-vascular mass in the nasopharynx area. Performing biopsy for histopathologic confirmation is necessary in the case of NPC or LEC NC but could be fatal in the case of angiofibroma. In our case, a 21-year-old male who was suffering from unilateral nasal stuffiness and frequent epistaxis had a mass with an easily bleeding tendency in his right nasal cavity. Juvenile angiofibroma was suspected by clinical and radiologic examinations. We performed preoperative angiography and the feeding vessel from the right internal maxillary artery was obliterated with polyvinyl alcohol nanoparticle. The mass was completely removed endoscopically, and there was profound hemorrhage in spite of the preoperative embolization. The mass turned out to be LEC NC by postoperative histopathologic examination. To avoid this misdiagnosis, the authors suggest that we should perform biopsy under rigid endoscopy 24h after angiographic embolization. If the result of frozen biopsy is juvenile angiofibroma, we could perform surgery another 24h later. If the result is nasopharyngeal carcinoma or LEC NC, we could avoid unnecessary surgical removal and perform radiotherapy. In terms of treatment strategies, we suggest endoscopic removal of gross tumor and postoperative combination of chemoradiotherapy as the more curative regimen with less complications related with radiotherapy.

Septoplasty improves life quality related to allergy in patients with septal deviation and allergic rhinitis.

OBJECTIVE: Evaluate the effect of septoplasty on the clinical course of allergic rhinitis by comparing (1) symptom change using the Visual Analogue Scale (VAS), (2) change of the medication score, and (3) improvement of the quality of life using a questionnaire. STUDY DESIGN: Prospective pilot. SETTING: Academic tertiary rhinological practice. SUBJECTS AND METHODS: Sixty-two patients who had undergone septoplasty and turbinoplasty for septal deviation and allergic rhinitis were enrolled in group A. Twenty-six patients who had undergone only turbinoplasty for allergic rhinitis were enrolled in group B. The VAS score, the Average Rescue Medication Score (ARMS), and the Rhinasthma Questionnaire for the quality of life were all obtained from each patient. These parameters were compared before and after the surgery and between the groups. RESULTS: Both groups showed significant improvement of the VAS score (P < .001). When the change of VAS was compared between groups, there was a significant difference in group A only for nasal obstruction (P = .047). Comparison of the ARMS between groups showed significant improvement in both groups after the surgery (P < .01). However, there were no differences between the groups. The Rhinasthma score of group A was significantly lowered after the surgery (56.4 ± 13.2 to 34.1 ± 12.3, P < .001). The Rhinasthma score of group A was significantly lower than that of group B after the surgery (P = .004). CONCLUSIONS: This is the first research about the potential effect of septoplasty on the clinical course of allergic rhinitis. Further studies are needed to elucidate the mechanisms underlying these effects.