Gut Dysbiosis and Abnormal Bile Acid Metabolism in Colitis-Associated Cancer.

BACKGROUND: Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. METHODS: C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. RESULTS: The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. CONCLUSION: Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.

Expression of C-X-C chemokine receptor type 7 in otorhinolaryngologic neoplasms.

INTRODUCTION: C-X-C chemokine receptor type 7 (CXCR7) has recently been characterised as a novel receptor for the C-X-C motif chemokine 12 (CXCL12)/stromal cell-derived factor 1-alpha. CXCR7 has been thought to play an important role in the pathogenesis of chronic rhinosinusitis, angiogenesis and tumour metastasis. The present study aimed to examine the expression of CXCR7 in tissue samples of laryngeal cancer and maxillary sinus carcinoma to determine its role in the development of otorhinolaryngologic neoplasms. METHODS: Samples of otorhinolaryngologic neoplasms were obtained from 17 patients with either nasal polyps (n = 7), laryngeal cancer (n = 5) or maxillary sinus carcinoma (n = 5), and who underwent surgical resection at West China Hospital of Sichuan University. Total RNA was isolated and CXCR7 mRNA expression was examined and quantified by relative real-time reverse transcription polymerase chain reaction. A one-way analysis of variance was performed using SPSS Statistics version 11.0 (SPSS Inc, Chicago, IL, USA) to compare the CXCR7 mRNA levels among the three groups of patients. RESULTS: All samples tested positive for CXCR7 mRNA. The quantitative results showed that the CXCR7 mRNA levels were highest in laryngeal cancer and lowest in maxillary sinus carcinoma neoplasms, although there was no significant difference among the three samples. CONCLUSION: CXCL12 and its receptor CXCR7 may contribute to eosinophilic inflammation in patients with chronic sinusitis and nasal polyps. Our results also suggest that CXCR7 may play a role in the progression, metastasis and angiogenesis of otorhinolaryngologic tumours.

[Chronic invasive fungal rhinosinusitis complicated with infratemporal fossa fungal infection: 2 cases report].

Two cases of chronic invasive fungal rhinosinusitis were reported. One patient healed while another died with suspicious residual fungal infection. The clinical symptoms of infratemporal fungal infection include maxillofacial pain, with or without fever. Acute or chronic inflammation of soft tissue could be revealed pathologically. Proof of pathogen may not be found in histopathological slice while serological detection may reveal positive evidence. Surgical resection, good drainage and postoperative antifungal therapy could cure or promptly relieve the symptoms of the disease.

[Correlation between patient-based questionnaires and computer tomography staging in chronic rhinosinusitis].

OBJECTIVE: To investigate the relationship between the patient-based questionnaires and the computed tomography (CT) staging in patients with chronic rhinosinusitis (CRS). METHODS: Quantitative data of 121 preoperative recruits with CRS were collected by using the Lund-Mackay CT staging system, a visual analogue scale (VAS), sino-nasal outcome test-20 (SNOT-20), and the medical outcome study short-form 36 items (SF-36). The patients were classified into several subgroups according to whether CRS was associated with nasal polyps (NP) or not, sex, duration of disease, and educational background. Correlation between the patient-based questionnaires and the CT staging were analyzed in the total cohort patients and subgroups. RESULTS: In the total cohort patients, there were significant correlations between SNOT-20 and SF-36 (r = -0.561, P < 0.01), SNOT-20 and VAS (r = 0.743, P < 0.01), and SF-36 and VAS (r = -0.504, P < 0.01), however, the CT staging did not correlate with the patient-based questionnaires (P > 0.05). Significant but weak correlations were found between the CT staging and the patient-based questionnaires in the CRS with NP subgroup (CT vs SNOT-20, r = 0.318, P = 0.005; CT vs SF-36, r = -0.358, P = 0.002; CT vs VAS, r = 0.358, P = 0.002). Compared between CRS with NP and without NP subgroup, there were statistic differences on the Lund-Mackay CT stage and the SNOT-20 and VAS scores (t value was 3.249, -2.409, -2.957, respectively, all P < 0.05). CONCLUSIONS: The patient-based questionnaires correlate well with each other, but CT staging correlated significantly but weakly with the patient-based questionnaires only in the CRS with NP subgroup. Nasal polyps do not appear to be responsible for the adverse effects of CRS on quality of life.

[Resection of anterior skull base cranio-nasal communication tumors via the inner plate of frontal sinus-epidural approach].

OBJECTIVE: To explore the application of inner plate of frontal sinus-epidural approach in the treatment of anterior skull base cranio-nasal communication tumors. METHOD: A study of 6 cranio-nasal communication tumor patients was undertaken. They were treated with lateral rhinotomy-inner plate of frontal sinus-epidural approach to remove tumor. RESULT: The tumors in all the 6 patients were completely resected. The follow-up study during the following 2 years revealed that 5 patients had good facial appearances and showed no tumor recurrence, no cerebrospinal rhinorrhea, no meningoencephalocele, no frontal collapse, and other complications. CONCLUSION: The surgical approach in the treatment of Cranio-nasal communication tumors needs to be chosen according to the tumor size, location and nature. Lateral rhinotomy-inner plate of frontal sinus-epidural approach can be carried out independently by the head and neck surgeons. It is a valuable surgical treatment with minimal invasion, short surgery time, little damage to brain, and easy pyrosis of skull base.

Expression of TGF, matrix metalloproteinases, and tissue inhibitors in Chinese chronic rhinosinusitis.

BACKGROUND: To date there is no information on the expression of mediators associated with tissue remodeling in Asian patients with chronic rhinitis with (CRSwNP) or without (CRSsNP) nasal polyps. OBJECTIVES: To study the expression of TGF-beta1, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), collagen, and regulatory T cells in Chinese patients with CRSwNP and CRSsNP. METHODS: Thirty-six male and female subjects (12 patients with CRSwNP, 12 patients with CRSsNP, and 12 control subjects), age 17 to 60 years, were recruited into the study. Samples were collected from polyp and sinusoidal mucosal, ethmoidal mucosal, or inferior turbinate in the respective groups and assessed for TGF- beta1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 by immunoassay; collagen by histochemistry; and forkhead box P3 (FOXP3) mRNA by real-time PCR. RESULTS: Patients with CRSwNP showed significantly lower concentrations of TGF-beta1, TIMP-1, TIMP-4, FOXP3, and collagen compared with patients with CRSsNP. Although there were no significant differences between the concentrations of MMP-7 and MMP-9 in patients with CRSwNP and CRSsNP, these were significantly increased compared with control patients. MMP-2 and TIMP-2 concentrations were not significantly different in any patient group, whereas TIMP-3 was not detectable. CONCLUSION: Chronic rhinosinusitis with nasal polyps is characterized by a relative lack of TGF-ss expression versus CRSsNP. This finding may be causal for decreased collagen, TIMP-1/4, and FOXP3 expression in CRSwNP versus CRSsNP. TGF-ss serves as a main switch for different remodeling patterns in sinus disease.

Correlation between computed tomography staging and quality of life instruments in patients with chronic rhinosinusitis.

BACKGROUND: Because chronic rhinosinusitis (CRS) is one of the most common health conditions in humans, it is important to assess its impact on quality of life (QoL). This study investigated the relationship between the findings of computed tomography (CT) staging and a patient-based questionnaire for CRS patients in Western China. METHODS: In this prospective study, the Lund-MacKay CT staging system, a visual analog scale (VAS), the 20-Item Sinonasal Outcome Test (SNOT-20), and the Short Form 36 Health Survey (SF-36) were completed for all preoperative recruits. The patients were classified into several subgroups according to whether CRS was associated with nasal polyps (CRS with nasal polyps [CRSwNPs]) or not (CRS without nasal polyps [CRSsNPs]), sex, duration of disease, and educational background. RESULTS: A total of 121 patients were recruited. In the total cohort of patients, there were significant correlations between scores on SNOT-20 and SF-36 (r = -0.561; p < 0.01), SNOT-20 and VAS (r = 0.743; p < 0.01), and SF-36 and VAS (r = -0.504; p < 0.01). Significant but weak correlations were found between the CT stage and scores on the patient-based questionnaires in the CRSwNP subgroup (CT versus SNOT-20, r = 0.31 and, p = 0.005; CT versus SF-36, r = -0.358 and p = 0.002; CT versus VAS, r = 0.358 and p = 0.002). The CT stage did not correlate with the scores in the patient-based questionnaires in the total cohort of patients. However, the CT stage was higher in the CRSwNP subgroup than in the CRSsNP, but QoL was better in the CRSwNP subgroup than in the CRSsNP subgroup. The two groups differed on the Lund-MacKay stage and the SNOT-20 and VAS scores (p < 0.05). CONCLUSION: The scores on patient-based questionnaires such as the SNOT-20, SF-36, and VAS correlate with each other. The CT stage correlated weakly but significantly with the scores in the patient-based questionnaires only in the CRSwNP subgroup. The presence of nasal polyps was not associated with poor QoL in CRS patients.

Inhibition of ataxia-telangiectasia mutated by antisense oligonucleotide nanoparticles induces radiosensitization of head and neck squamous-cell carcinoma in mice.

Ataxia-telangiectasia-mutated (ATM) is a radiosensitization gene. In the present study, we investigated the efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing ATM antisense oligonucleotides (ASOs) for the radiosensitization of head and neck squamous-cell carcinoma in mice, using the SCCVII cell line. Nanoparticles containing ATM ASOs were prepared with PLGA by using a double-emulsion solvent evaporation method. The results showed that the nanoparticles were suitable for intracellular uptake, and ATM ASOs inhibited ATM expression when delivered by using nanoparticles or lipofectin, but not in their free form. Meanwhile, we found that ATM reduction sensitized SCCVII cells in vitro and tumors in vivo to irradiation. In conclusion, biodegradable PLGA nanoparticles, used as a delivery carrier, enhanced intracellular uptake of ATM ASOs into SCCVII cells and the inhibitory effect of ATM ASOs. These results demonstrated that antisense ATM therapy, using PLGA nanoparticles, might provide a therapeutic benefit to patients undergoing radiation therapy for head and neck squamous-cell carcinoma.

Antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous cell carcinoma in mice.

BACKGROUND: Treatment failure after radiotherapy of head and neck squamous cell carcinoma (HNSCC) could be a significant problem. Our objective is to sensitize SCCVII cells to ionizing radiation in vitro and in vivo through inhibiting ATM expression using antisense oligodeoxynucleotides (AS-ODNs), and investigate the potential mechanism of radiosensitization. METHODS: We designed and synthesized AS-ODNs that target ATM mRNA to reduce the ATM expression. The influence on the expression of ATM mRNA and protein in SCCVII cells were analysed by real-time quantitative PCR and western blotting respectively. Clonogenic survival assay was performed to detect the survival ability of SCCVII cells after irradiation, while flow cytometry used to analyse the cell cycle and apoptosis. The volume of solid tumors generated with SCCVII cells was measured, and cell apoptosis was analysed by TUNEL assay after irradiation. RESULTS: The relative ATM mRNA and protein expression in SCCVII cells treated with ATM AS-ODNs were decreased to 25.7 +/- 3.1% and 24.1 +/- 2.8% of that in untreated cells respectively (P < 0.05). After irradiation, the survival fraction (SF) of cells treated with ATM AS-ODNs was lower than that of other groups at the same dose of radiation (P < 0.05), while the percentage of cells in G2/M phase decreased and apoptotic rate of cells increased (P < 0.05). The inhibition rate in SCCVII cells solid tumor exposed to X-ray alone was 23.2 +/- 2.7%, while it was 56.1 +/- 3.8% in the group which irradiated in combination with the treatment of ATM AS-ODNs (P < 0.05). The apoptotic index for the group irradiated in combination with ATM AS-ODNs injection was 19.6 +/- 3.2, which was significantly higher than that of others (P < 0.05) CONCLUSION: Inhibition of ATM expression sensitized SCCVII cells to ionizing radiation in vitro and in vivo. The potential mechanism should be the defective G2/M cell cycle checkpoint control and enhanced radiation-induced apoptosis.

[Early outcome of one-stage transnasal surgery combined with transnasal surgery for cranionasal tumors and reconstruction of skull base].

OBJECTIVE: To investigate the microsurgical management of cranionasal tumors and the method of the reconstruction of the skull base. METHODS: From June 2005 to October 2007, 20 patients with cranionasal tumor were treated. There were 10 males and 10 females, aged between 13 and 77 years (median 49 years). The disease course was 2 months to 13 years. The cranionasal tumors, proved by MRI and CT scans, located in the anterior skull base, paranasal sinus, nasal and/or orbit cavity. And their clinical presentations were listed as follows: dysosphresia in 14 patients, headache in 11 patients, nasal obstruction in 9 patients, epistaxis in 8 patients, visual disorder in 4 patients, exophthalmos in 4 patients and conscious disturbance in 2 patients. All 20 patients underwent transnasal surgery combined with transnasal surgery, and tumors were resected by one-stage operation. The skull base was reconstructed by surgical technique "Pull Down Sandwich" with pedicle periosteum flap. RESULTS: Tumors were resected by one-stage operation, and the anterior skull bases were reconstructed. Pathological examination showed 8 cases of malignant tumors and 12 cases of benign tumors. The total surgical excision was complete in 16 patients, and 4 patients with subtotal excision. There was no operative death. Eighteen patients were followed up 3 months to 2 years and 6 months. Transient cerebrospinal fluid rhinorrhea was found in 2 cases which were cured by lumbar drainage. And recurrence of tumor was observed in 5 patients 3 months to 2 years after operation. CONCLUSION: Microsurgical operation via subfrontal approach assisted by transnasal endoscopy is an effective method in management of cranionasal tumors, with the advantages of reconstruction of the skull base with pedicle periosteum flap or "Pull Down Sandwich" and low complication rate.

[Micro-neurosurgical treatment of cranionasal tumors in combination with transnasal endoscopy].

OBJECTIVE: To explore an effective microsurgical approach to the treatment of cranionasal tumors. METHODS: A retrospective review of 18 micro-neurosurgical patients with cranionasal tumors (June 2005 to June 2007) was undertaken. RESULTS: All of the 18 patients were treated with subfrontal approaches in combination with transnasal endoscopy. Tumors were resected in the stage-one operations (14 were totally resected and 4 were subtotally resected). The anterior skull bases were reconstructed. Transient CSF rhinorrhea was found in two cases. All of the patients experienced good recoveries, with no operative death. The follow up after 5 to 29 months revealed that only four patients had tumor recurrence. Three patients lost in the follow up. CONCLUSION: Subfrontal microsurgical operation combined with transnasal endoscopy is an effective approach to the treatment of cranionasal tumors. It enables high total resection rate and has low complications.

[Endoscopic repair of cerebrospinal fluid rhinorrhea].

OBJECTIVE: To investigate the best treatment of cerebrospinal fluid rhinorrhea. METHOD: A retrospective study of 45 consecutive patients who presented with CSF leak,was conducted. Forty-two patients were treated with transnasal endoscopic approach, three with double approach transnasal and extranasal. The fascia lata, the myoplasm, the free middle turbinate graft and the free inferior turbinate graft were used for fistula repairing. Four repair techniques as onlay technique, inlay technique, underlay technique and obliteration technique were used. RESULT: Postoperative follow-up lasted from 5 to 84 months. The overall success rate after the first operation was 97.8%. Three patients got meningitis,one patient got local infection in frontal sinus, but all of them were cured. CONCLUSION: In our study, The outcome was very good in endoscopic repair of a small fistula in anterior cerebrospinal, a fistula in dorsum delta and a fistula in slope with a free graft of autogenous. But it needed a perfect choose in operation approach, repair technique and graft material.

[Deep neck abscess: analysis of 50 cases].

OBJECTIVE: To identify the predisposing factors of deep neck abscess and review diagnosis and treatment experience. METHODS: A respective review was conducted in 50 cases who were diagnosed as having deep neck abscess in this hospital from Jan. 1997 to Dec. 2002. RESULTS: The causes of deep neck abscess were tooth diseases (3 cases), acute tonsillitis and laryngitis (8 cases), infection of upper respiratory tract (9 cases), foreign bodies in esophagus (14 cases), diabetes mellitus (5 cases), uncertain cause (11 cases). Among 21 cases of pus bacterial cultivation, 13 (64%) cases were positive. By different ways of drainage including neck-mediastinum incision, and use of large dosage of antibiotics, 46 six cases were cured and 4 cases died. Two died of massive hemorrhage of neck blood vessel burst, one massive hemorrhage of upper digestive tract, another infective shock. CONCLUSIONS: Once deep neck abscess is diagnosed, early surgical drainage, appropriate use of antibiotics and control of complications and accompanying diseases are very important to improve the cure rate.