The cardiovascular system at high altitude: A bibliometric and visualization analysis.

BACKGROUND: When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM: To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS: The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS: A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION: Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database.

PURPOSE: We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.). MATERIALS AND METHODS: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. RESULTS: 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245-0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0-48 hours vs. 48-53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. CONCLUSION: EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

A comparative transcriptomic analysis reveals a coordinated mechanism activated in response to cold acclimation in common vetch (Vicia sativa L.).

BACKGROUND: Due to its strong abiotic stress tolerance, common vetch is widely cultivated as a green manure and forage crop in grass and crop rotation systems. The comprehensive molecular mechanisms activated in common vetch during cold adaptation remain unknown. RESULTS: We investigated physiological responses and transcriptome profiles of cold-sensitive (Lanjian No. 1) and cold-tolerant (Lanjian No. 3) cultivars during cold acclimation to explore the molecular mechanisms of cold acclimation. In total, 2681 and 2352 differentially expressed genes (DEGs) were identified in Lanjian No. 1 and Lanjian No. 3, respectively; 7532 DEGs were identified in both lines. DEGs involved in "plant hormone signal transduction" were significantly enriched during cold treatment, and 115 DEGs involved in cold-processed hormone signal transduction were identified. Common vetch increased the level of indoleacetic acid (IAA) by upregulating the transcriptional regulator Aux/IAA and downregulating GH3, endowing it with stronger cold tolerance. An auxin-related DEG was overexpressed in yeast and shown to possess a biological function conferring cold tolerance. CONCLUSION: This study identifies specific genes involved in Ca2+ signaling, redox regulation, circadian clock, plant hormones, and transcription factors whose transcriptional differentiation during cold acclimation may improve cold tolerance and contributes to the understanding of common and unique molecular mechanisms of cold acclimation in common vetch. The candidate genes identified here also provide valuable resources for further functional genomic and breeding studies.

Effect of Glut-1 and HIF-1α double knockout by CRISPR/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K/Akt/mTOR pathway.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18 F-fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia-induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF-1α and Glut-1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF-1α and/or Glut-1 in the presence of irradiation. HIF-1α and/or Glut-1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF-1α and/or Glut-1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF-1α and Glut-1. HIF-1α and/or Glut-1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF-1α and/or Glut-1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.

Targeted Inhibition of HK-II Reversed the Warburg Effect to Improve the Radiosensitivity of Laryngeal Carcinoma.

PURPOSE: Hexokinase-II (HK-II) is the key enzyme in the first rate-limiting step of glycolysis that catalyzes the conversion of glucose to glucose-6-phosphate. Here, we examined the association between HK-II expression and radioresistance in laryngeal carcinoma and whether the inhibition of HK-II expression can enhance the radiosensitivity of these tumors. METHODS: The effects of HK-II small interfering RNA (siRNA) on the radiosensitivity of Tu212 cells were examined in vitro and in vivo in a mouse model. Cells were irradiated using a 6-MV linear accelerator. The cell viability, cell survival, proliferation, apoptosis, and cell cycle of Tu212 cells were evaluated using trypan blue staining, colony formation assays, CCK-8 assays, and flow cytometry, respectively. Oxygen consumption, lactic acid production, glucose consumption, and the ATP level of Tu212 cells were also examined. The expression of glycolytic and regulatory enzymes involved in the tricarboxylic acid cycle was assessed using Western blotting. RESULTS: The HK-II siRNA and X-ray combination treatment led to a significantly greater reduction of cell viability, inhibition of cell survival and proliferation, increased apoptosis, and increased G2 phase arrest compared to either treatment alone (all, P<0.01). HK-II siRNA increased the oxygen consumption rate of cells, significantly inhibited lactic acid production and glucose consumption, and significantly suppressed the upregulation of HK-II, pyruvate kinase M2 (PKM2), pyruvate dehydrogenase (PDH), phosphofructokinase platelet (PFKP), lactate dehydrogenase (LD), and citrate synthase (CS) (all, P<0.01). CONCLUSION: The inhibition of HK-II by siRNA enhances the radiosensitivity of laryngeal carcinoma Tu212 cells by inhibiting glycolysis and partially inhibiting oxidative phosphorylation.

Radiosensitizing effects of curcumin alone or combined with GLUT1 siRNA on laryngeal carcinoma cells through AMPK pathway-induced autophagy.

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy-related proteins in LC and that curcumin suppressed radiation-mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6-amino-3-methypourine (3-MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3-MA inhibited curcumin and GLUT1 siRNA-mediated non-apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3-MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP-activated protein kinase-mTOR-serine/threonine-protein kinase-Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.

Effect of combination of curcumin and GLUT-1 AS-ODN on radiosensitivity of laryngeal carcinoma through regulating autophagy.

BACKGROUND: This study is to explore the role of curcumin and GLUT-1 antisense oligodeoxynucleotides (AS-ODN) on autophagy modulation-initiated radiosensitivity. METHODS: BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy- and apoptosis-related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining. RESULTS: Combinations of curcumin and GLUT-1 AS-ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3-MA also had a promotion effect on irradiation-mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT-1 AS-ODN-mediated growth inhibition potentially by regulating autophagic events. Of note, a de-escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT-1 AS-ODN or 3-MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone. CONCLUSIONS: Curcumin and GLUT-1 AS-ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.

GLUT-1 siRNA Enhances Radiosensitization Of Laryngeal Cancer Stem Cells Via Enhanced DNA Damage, Cell Cycle Redistribution, And Promotion Of Apoptosis In Vitro And In Vivo.

BACKGROUND: Radiotherapy does not show good efficacy against laryngeal cancer due to radioresistance. Cancer stem cells (CSCs) are considered among the causes of radioresistance. Inhibition of glucose transporter-1 (GLUT-1) using GLUT-1 small interfering RNA (siRNA) may enhance the radiosensitivity of laryngeal cancer cells, but the underlying cellular mechanisms remain unclear. METHODS: The CD133+-Hep-2R cell line was established with repeated irradiation and magnetic-activated cell sorting. The effects of irradiation on CD133+-Hep-2R cells were examined by CCK-8 assay, Transwell assay, quantitative real-time polymerase chain reaction (RT-PCR), and Western blotting. The effects of GLUT-1 siRNA on the radiosensitivity of CD133+-Hep-2/2R cells were examined by RT-PCR, Western blotting, CCK-8 assay, colony formation assay, and Transwell assay in vitro and in a xenograft tumor model in nude mice. The cellular mechanism of enhanced radiosensitivity associated with GLUT-1 siRNA was investigated. The cell cycle and apoptosis rate were analyzed by flow cytometry, and the repair capability was examined by determining the levels of RAD51 and DNA-PKcs. RESULTS: CD133+-Hep-2/2R cells showed stronger proliferation, lower apoptosis rate, lower percentage of G0/G1 phase cells, higher percentages of S and G2/M phase cells, and higher expression levels of GLUT-1 than Hep-2/2R cells. Transfection with GLUT-1 siRNA inhibited the proliferation and invasive capability of CD133+-Hep-2R cells by inhibiting GLUT-1 expression, which also caused a redistribution of the cell cycle (higher proportion of cells in the G0/G1 phase and lower proportion in the S and G2/M phases), increased the apoptosis rate, and reduced DNA repair capability by suppressing RAD51 and DNA-PKcs expression. CONCLUSION: The results of this study suggest that GLUT-1 siRNA can enhance the radiosensitivity of CD133+-Hep-2R cells by inducing a redistribution of cell cycle phases, inhibiting DNA repair capability, and increasing apoptosis. Inhibition of GLUT-1 may have therapeutic potential for interventions to increase the radiosensitivity of laryngeal CSCs.

Construction of a GLUT-1 and HIF-1α gene knockout cell model in HEp-2 cells using the CRISPR/Cas9 technique.

BACKGROUND: Glucose transporter (GLUT)-mediated glucose uptake is an important process in the development of laryngeal carcinoma, one of the most common malignancies of the head and neck. GLUT-1, together with HIF-1α, is also an indicator of hypoxia. Both proteins play a critical role in glucose uptake and glycolysis in laryngeal carcinoma cells under hypoxic stress. A double gene knockout model in which HIF-1α and GLUT-1 are no longer expressed can provide important information about carcinogenesis in laryngeal carcinoma. PURPOSE: In this study we used the CRISPR/Cas 9 system to induce HIF-1α and GLUT-1 double gene knockout in HEp-2 cells and then used the knocked-out cells to study the role of these markers in laryngeal carcinoma, including in chemoradioresistance. METHODS: High-grade small-guide RNAs (sgRNAs) of HIF-1α and GLUT-1 were designed using an online tool and inserted into the pUC57-T7-gRNA vector. The recombinant plasmids were transfected into HEp-2 cells and positive cells were screened using the dilution method. Gene mutation and expression were determined by sequence analysis and immunoblotting. RESULTS: In HIF-1α and GLUT-1 double gene knockout HEp-2 cells, a 171-bp deletion in the HIF-1α genomic sequence was detected, whereas multiple base insertions resulted in frameshift mutations in the GLUT-1 gene. Neither HIF-1α nor GLUT-1 protein was expressed in positive cells. The proliferation, migration, and invasion of HEp-2 cells were significantly decreased afterward. The possible mechanism may be that the inhibition PI3K/AKT/mTOR pathway by HIF-1α and GLUT-1 double gene knockout using CRISPR/Cas9 technique lead to reduction of glucose uptake and lactic acid generation. CONCLUSION: Our HIF-1α and GLUT-1 double gene knockout HEp-2 cell model, obtained using a CRISPR/Cas9-based system, may facilitate studies of the pathogenesis of laryngeal carcinoma.

In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal carcinoma using micro 18F-FDG PET/CT.

PURPOSE: Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo. MATERIALS AND METHODS: To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-2 (2 × 107/mL × 0.2 mL) and Tu212 cells (2 × 107/mL × 0.2 mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 µg) and GLUT-1 AS-ODNs (100 µg) on the radiosensitivity of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated and the value of 18F-FDG-PET/CT was assessed after treating the xenografts. RESULTS: 10 Gy X-ray irradiation decreased the weight of Hep-2 xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-2 xenografts 8 days after treatment (p < 0.05) and in Tu212 xenografts 12 days after treatment (p < 0.001). Standardized uptake value (tumor/normal tissue)( SUVmaxT/N) did not show a statistically significant correlation with GLUT1 and HIF-1α expression and therapeutic effect (necrosis, apoptosis). CONCLUSIONS: Simultaneous inhibition of HIF-1α and GLUT-1 expression might increase the radiosensitivity of laryngeal carcinoma, decreasing MVD, and promoting apoptosis and necrosis. 18F-FDG-PET/CT wasn't useful in evaluating the therapeutic effect on laryngeal cancer in this animal study.

In-vivo organ engineering: Perfusion of hepatocytes in a single liver lobe scaffold of living rats.

Organ decellularization is emerging as a promising regenerative medicine approach as it is able to provide an acellular, three-dimensional biological scaffold material that can be seeded with living cells for organ reengineering. However this application is currently limited to donor-derived decellularized organs for reengineering in vitro and no study has been conducted for re-engineering the decellularized organ in vivo. We developed a novel technique of a single liver lobe decellularization in vivo in live animals. Using a surgical method to generate a by-pass circulation through the portal vein and infra-hepatic vena cava with a perfusion chamber system, we decellularized the single liver lobe and recellularized it with allogenic primary hepatocytes. Our results showed that the decellularization process in vivo can preserve the vascular structural network and functional characteristics of the native liver lobe. It allows for efficient recellularization of the decellularized liver lobe matrix with allogenic primary hepatocytes. Upon the re-establishment of blood circulation, the recellularized liver lobe is able to gain the function and the allogenic hepatocytes are able to secret albumin. Our findings provide a proof of principle for the in vivo reengineering of liver.

Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo.

In the present study, we investigated the role of GLUT-1 and PI3K/Akt signaling in radioresistance of laryngeal carcinoma xenografts. Volume, weight, radiosensitization, and the rate of inhibition of tumor growth in the xenografts were evaluated in different groups. Apoptosis was evaluated by TUNEL assay. In addition, mRNA and protein levels of GLUT-1, p-Akt, and PI3K in the xenografts were measured. Treatment with LY294002, wortmannin, wortmannin plus GLUT-1 AS-ODN, and LY294002 plus GLUT-1 AS-ODN after X-ray irradiation significantly reduced the size and weight of the tumors, rate of tumor growth, and apoptosis in tumors compared to that observed in the 10-Gy group (p<0.05). In addition, mRNA and protein expression of GLUT-1, p-Akt, and PI3K was downregulated. The E/O values of LY294002, LY294002 plus GLUT-1 AS-ODN, wortmannin, and wortmannin plus GLUT-1 AS-ODN were 2.7, 1.1, 1.8, and 1.8, respectively. Taken together, these data indicate that GLUT-1 AS-ODN as well as the inhibitors of PI3K/Akt signaling may act as radiosensitizers of laryngeal carcinoma in vivo.

Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo.

Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is an important hypoxic marker in malignant tumors, including laryngeal carcinoma. Apigenin is a natural phytoestrogen flavonoid that has potential anticancer effects. Various studies have reported that the effects of apigenin on lowering GLUT-1 expression were involved in downregulation of the PI3K/Akt pathway. Thus, apigenin may improve the radiosensitivity of laryngeal carcinoma by suppressing the expression of GLUT-1 via the PI3K/Akt pathway. The effect of GLUT-1 and PI3K/Akt pathway-related factor expressions by apigenin or antisense oligonucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vivo was assessed. The xenograft volume, xenograft weight and apoptosis detection were performed to determine radiosensitivity. The results showed that apigenin or apigenin plus GLUT-1 AS-ODNs improved the radiosensitivity of xenografts. Apigenin or apigenin plus GLUT-1 reduced the expression of GLUT-1, Akt, and PI3K mRNA after X-ray radiation. We found similar results at the protein level. The results suggest that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism.

Follicular dendritic cell sarcoma of the right tonsil: A case report and literature review.

The current study presents a case of extranodal follicular dendritic cell sarcoma (FDCS) of the tonsil and reviews the relevant literature. In the present case, a 59-year-old male presented with a globus sensation in the right pharynx for 6 weeks. On clinical examination, a painless non-ulcerated enlarged right tonsil was identified; the tonsil was covered with a normal mucus membrane. A right tonsillectomy was performed under general anesthesia. The final pathological diagnosis was follicular dendritic cell sarcoma of the right tonsil. Postoperatively, the patient received radiotherapy. The patient remains alive without disease recurrence or metastasis 44 months after tonsillectomy. To the best of our knowledge, only 42 cases of FDCS of the tonsil have been reported to date. Of the 42 cases, 41 patients underwent surgery and one patient refused treatment. A total of 23 (54.7%) received surgery alone. Adjuvant treatment was administered for 18 patients (42.9%). Six patients (14.3%) experienced local recurrences and two patients (4.8%) succumbed to the disease 24 months after treatment. The three-, five-, and eight-year overall survival rates for the entire group were 86.5, 77.8 and 77.8%, respectively. Furthermore, a tumor diameter of ≥4 cm was prognostic upon univariate analysis (χ2=4.634; P=0.031; excluding incomplete data). Tonsillar FDCS is rare and is associated with high rates of recurrence and metastasis, therefore, adjuvant treatment should be prescribed.

Metastatic squamous cell carcinoma of the gingiva appearing as a solitary branchial cyst carcinoma: diagnostic role of PET/CT.

We herein present a case of a left cervical cystic mass, for which the initial pathological diagnosis was branchial cleft cyst carcinoma (following complete mass excision). Thorough postoperative examinations, including with FDG positron emission tomography/computed tomography (PET/CT), revealed a primary tumor in the retromolar region of the left mandible. A 52-year-old female presented with a 2-month history of a painless, progressively enlarged left-sided neck mass. Fine-needle aspiration biopsy suggested a branchial cleft cyst. Physical examination revealed a 3 × 3-cm smooth, tender mass in the upper-left neck and anterior border of the sternocleidomastoid muscle. Examination using nasendoscopy and a strobolaryngoscope revealed no abnormalities of the nasal cavity, nasopharynx, oropharynx, hypopharynx or larynx. MRI of the neck revealed a solitary, round, cystic mass under the left parotid gland. The mass was excised completely. Pathologic results indicated a branchial cleft cyst carcinoma. According to the diagnostic criteria for a branchial cleft cystic carcinoma, PET/CT was performed to detect the occult primary site. PET/CT revealed high FDG uptake in the tooth root of the left mandible. Frozen sections of the mass were indicative of moderate, differentiated squamous cell carcinoma. The carcinoma in the retromolar region of the left mandible was locally excised under general anesthesia. A partial left maxillectomy, partial mandibulectomy, and left radical neck dissection were performed. The patient received postoperative concurrent chemoradiotherapy, and was disease-free at the 8-month follow-up. True branchial cleft cyst carcinoma is rare: once diagnosed, it should be distinguished from metastatic cystic cervical lymph and occult primary carcinoma. FDG PET/CT is useful in the identification of occult primary tumor.

Role of PET/CT in the diagnosis, staging, and follow-up of a nasal-type natural killer T-cell lymphoma in the larynx: a case report and literature review.

BACKGROUND: Nasal-type natural killer T-cell lymphoma involving the larynx is uncommon. Our search revealed only 12 cases reported previously in the English-language literature. CASE REPORT: We report a case of laryngeal NKTCL. In December 2011, the patient was diagnosed with nasal-type NKTCL and FDG PET/CT showed the lesions were confined to the nasal cavity (stage I). At 1 year after radiotherapy, the patient presented with hoarseness and FDG PET/CT revealed high FDG uptake in the subglottic region and left cervical lymph nodes. A biopsy of the subglottis confirmed NKTCL (stage II). He then received chemotherapy and 14 months after the completion of chemotherapy, FDG PET/CT showed no evidence of recurrence or metastasis. CONCLUSIONS: PET/CT has better sensitivity than other conventional methods and may play an important role in the diagnosis, staging, and follow-up of nasal-type natural killer T-cell lymphoma.

Expression of hypoxia-related markers in inflammatory myofibroblastic tumors of the head and neck.

BACKGROUND: The etiology of inflammatory myofibroblastic tumors (IMTs) is controversial and the prognosis is unpredictable. Previous studies have not investigated the expression of hypoxia-related markers in IMTs. METHODS: Between 2002 and 2012, 12 consecutive patients with histologically proven IMTs were enrolled in the study. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin-embedded tumor specimens. Associations among GLUT-1, HIF-1α, PI3K, and p-Akt protein expression and clinical parameters were investigated. RESULTS: The mean duration of follow-up was 52.1 months (range, 11 to 132 months). Six patients had local recurrence. GLUT-1, HIF-1α, PI3K, and p-Akt expression were detected in 41.7%, 50.0%, 33.3%, and 41.7% of patients, respectively. Fisher's exact test revealed significant correlations between recurrence of IMT and PI3K expression (P = 0.01) and p-Akt expression (P = 0.015). Univariate analyses revealed significant correlations between survival and GLUT-1 expression (P = 0.028), PI3K expression (P = 0.006), and p-Akt expression (P = 0.028). Multivariate analysis did not show a significant relationship between survival and GLUT-1, HIF-1α, PI3K, or p-Akt. Spearman rank correlation analysis showed significant correlations between HIF-1α and PI3K expression (r = 0.707, P = 0.01) and between p-Akt and PI3K expression (r = 0.837, P = 0.001). CONCLUSIONS: Although our results are inconclusive owing to the small sample size, they suggest that PI3K and p-Akt expression may play a role in the recurrence of IMTs of the head and neck.

Effect of antisense oligodeoxynucleotides glucose transporter-1 on enhancement of radiosensitivity of laryngeal carcinoma.

PURPOSE: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. METHODS: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. RESULTS: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). CONCLUSION: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1.

¹8F-fluorodeoxyglucose positron emission tomography/computed tomography as an effective diagnostic workup in cervical metastasis of carcinoma from an unknown primary tumor.

PURPOSE: The purpose of this study is to assess the potential of ¹8F-fluorodeoxyglucose (¹8FDG) positron emission tomography/computed tomography (PET/CT) imaging for the diagnosis of cervical metastasis of carcinoma of an unknown primary tumor (CUP) and to determine whether the maximum standardized uptake value (SUV(max)) is a prognostic factor. METHODS: Twenty-five consecutive patients with cervical metastasis of CUP were retrospectively analyzed by PET/CT between July 2007 and July 2011. RESULTS: FDG PET/CT suggested a primary tumor in 21 out of 25 patients (84.0%). The sensitivity of FDG PET/CT in detecting the primary tumor was 73.3% (11 of 15), and the positive predictive value was 52.4% (11 of 21). The median follow-up duration of survival patients was 10.4 months (range: 0-30 months). The estimated 2-year overall survival rate of all patients was 50.0%. Univariate analyses did not reveal a significant difference in overall survival between the group of 11 patients identified by pathology and the 14 patients not identified by pathology (overall survival was 57.1% and 49.1%, respectively; p=0.468). The median SUV(max) was 7.6. In the log-rank test, patients with a low SUV(max) (≤ 7.0) in cervical lymph nodes had a significantly higher survival rate at 2 years (87.5% vs. 21.2%; p=0.007) than patients with a high SUV(max) (>7.0). CONCLUSIONS: Although our study was inconclusive due to the small sample size, our results suggest that FDG PET/CT may be an effective diagnostic workup in the cervical metastasis of carcinoma from an unknown primary tumor (UPT). In the present study, SUV(max) of PET/CT in the cervical lymph node may serve as a prognostic factor of cervical metastasis of carcinoma from a UPT based on the limited number of patients. Further studies are needed to confirm these findings.