Recognition of 8-Oxo-2'-deoxyguanosine in DNA Using the Triphosphate of 2'-Deoxycytidine Connecting the 1,3-Diazaphenoxazine Unit, dCdapTP.

DNA is constantly damaged by various external and internal factors. In particular, oxidative damage occurs in a steady state, and 8-oxo-2'-deoxyguanosine (oxodG) is known as the main oxidative damage. OxodG is a strong genotoxic nucleoside and is thought to be involved in the pathogenesis of cancer and neurological diseases. However, a breakthrough method to detect the position of oxodG in DNA has not yet been developed. Therefore, we attempted to develop a novel method to detect oxodG in DNA using artificial nucleosides. Recently, we have succeeded in the recognition of oxodG in DNA by a single nucleotide elongation reaction using nucleoside derivatives based on a purine skeleton with a 1,3-diazaphenoxazine unit. In this study, we developed a new nucleoside derivative with a pyrimidine skeleton in order to further improve the recognition ability and enzymatic reaction efficiency. We, therefore, designed and synthesized 2'-deoxycytidine-1,3-diazaphenoxazine (Cdap) and its triphosphate derivatives. The results showed that it was incorporated into the primer strand relative to the dG template because of its cytidine skeleton, but it was more effective at the complementary position of the oxodG template. These results indicate that the new nucleoside derivative can be considered as one of the new candidates for the detection of oxodG in DNA.

Unusually elongated superior thyroid cornu associated with recurrent cerebral embolisms.

The superior thyroid cornu (STC) is a normal anatomic structure that forms part of the thyroid cartilage. Here, we report a patient with unusually elongated and ossified STC that might result in recurrent cerebral embolisms. During a second endovascular therapy for recurrent middle cerebral artery embolism, a segment with an irregular filling defect was noted in the internal carotid artery (ICA), at the C1 level. This defect was unnoticed during the initial endovascular procedure. Three-dimensional computed tomography angiography performed after the second endovascular procedure revealed an ICA segment located between the STC and C1 with a tortuous course and irregular wall of the ICA. Therefore, we assumed that STC compression of the ICA could have resulted in thrombus formation at the site and consequent cerebral embolism. The STC should be considered a structure responsible for cerebral embolism. Careful evaluation of the entire ICA course is imperative prior to performing an endovascular thrombectomy for acute embolic occlusion of the middle cerebral artery.

Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

Selective Unnatural Base Pairing and Recognition of 2-Hydroxy-2'-deoxyadenosine in DNA Using Pseudo-dC Derivatives.

The formation of unnatural base pairs within duplex DNA would facilitate DNA nanotechnology and biotechnology. Iso-2'-deoxyguanosine (iso-dG) forms base pairs with iso-2'-deoxycytidine, and its use as an unnatural base pair was investigated. Iso-dG is one of the tautomers of 2-hydroxy-2'-deoxyadenosine (2-OH-dA), known as an oxidatively damaged nucleobase, and its selective recognition in DNA plays an important role in the diagnosis and pathogenesis of disease. Therefore, we focused on pseudo-dC (ψdC) as a suitable molecule that recognizes 2-OH-dA in DNA. Since 2-OH-dA shows tautomeric structures in DNA, we designed and used ψdC, which also has a tautomeric structure. We successfully synthesized a ψdC phosphoramidite compound for the synthesis of oligonucleotides (ODNs) as well as its triphosphate derivative (ψdCTP). Tm measurements revealed that ODNs including ψdC showed stable base pair formation with ODNs having 2-OH-dA. In contrast, low Tm values were observed for other bases (dG, dA, dC, and T). The results obtained for the single-nucleotide primer extension reaction revealed that ψdCTP was incorporated into the complementary position of 2-OH-dA in template DNA with high selectivity. In addition, the primer elongation reaction was confirmed to proceed in the presence of dNTPs. The present study reports an artificial nucleic acid that selectively and stably forms unnatural base pairs with 2-OH-dA in DNA.

Are volume-dependent parameters in positron emission tomography predictive of postoperative recurrence after resection in patients with thymic carcinoma?

This study aimed to investigate the association between the volume-dependent parameters in 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) and a recurrence of thymic carcinoma. A retrospective chart review was performed based on our multi-institutional database to identify patients undergoing PET prior to resection of thymic carcinoma or neuroendocrine carcinoma between 1991 and 2018. The PET parameters (metabolic tumor volume and total lesion glycolysis) were evaluated retrospectively. The relevant factors were extracted and a survival analysis was performed using the Kaplan-Meier method. Sixteen patients were thus deemed to be eligible for analysis. The median follow-up period following resection was 2.65 years (range: 0.96-0.68 years). The recurrence-free survival was significantly longer in patients with a metabolic tumor volume < = 22.755 cm3 and with total lesion glycolysis < = 105.4006 g/mL (p = 0.001 and 0.001, respectively, by a log-rank test). The metabolic tumor volume and total lesion glycolysis may, therefore, be predictive of the postoperative recurrence of thymic carcinoma.

The treatment and survival of patients with postoperative recurrent thymic carcinoma and neuroendocrine carcinoma: a multicenter retrospective study.

PURPOSE: There are few data available on the outcomes of postoperative recurrent thymic carcinoma (TC) and thymic neuroendocrine carcinoma (TNEC). The aim of this study is to evaluate the treatment and survival in patients with recurrent TC and TNEC after undergoing surgical resection. METHODS: A retrospective chart review was performed using our multicenter database to identify patients with a postoperative recurrence of TC and TNEC from 1995 to 2018. The clinicopathological factors were reviewed and the survival outcomes were analyzed. RESULTS: Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8 months (range 0-144). The 5-year post-recurrence survival was 23% for the whole cohort. According to a univariable analysis, advanced stage [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.09-9.54], interval between primary surgery and recurrence (HR 0.97, 95% CI 0.95-0.99), any treatment for recurrence (HR: 0.27, 95% CI 0.13-0.58) and chemotherapy for recurrence (HR: 0.46, 95% CI 0.22-0.95) were significant factors related to post-recurrence survival. CONCLUSIONS: Chemotherapy rather than surgery appears to be the mainstay treatment for managing patients with postoperative recurrent TC and TNEC and it may also be considered in multidisciplinary management. Further studies with a larger sample size are required to confirm our findings.

Simple and Easy Synthesis of γ-Amido-dNTPs in Water and Their Polymerase Reaction Properties.

γ-Amido-modified 2'-deoxynucleoside triphosphates (dNTPs) and nucleoside triphosphates (NTPs) are becoming increasingly important as biological tools. We herein describe the simple and easy synthesis of γ-amido-dNTPs and -NTPs from commercially available corresponding dNTPs and NTPs in a one-pot reaction using water-soluble carbodiimide and ammonia solution. We examined the effects of synthesized γ-amido-dNTPs on the DNA polymerase reaction. The results obtained showed the incorporation of these derivatives into the DNA primer while maintaining nucleobase selectivity; however, their incorporation efficiency by DNA polymerase was lower than that of dNTP. This is the first study to demonstrate the successful synthesis of four sets of γ-amido-dNTPs and clarify their properties.

Ligand Design for Specific MHC Class I Molecules on the Cell Surface.

We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I) molecules on the cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. This strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed in autoimmune diseases.

A new test for evaluation of marginal cognitive function deficits in idiopathic normal pressure hydrocephalus through expressing texture recognition by sound symbolic words.

Introduction: The number of dementia patients is increasing with population aging. Preclinical detection of dementia in patients is essential for access to adequate treatment. In previous studies, dementia patients showed texture recognition difficulties. Onomatopoeia or sound symbolic words (SSW) are intuitively associated with texture impressions and are less likely to be affected by aphasia and description of material perception can be easily obtained. In this study, we aimed to create a test of texture recognition ability expressed by SSW to detect the presence of mild cognitive disorders. Methods: The sound symbolic words texture recognition test (SSWTRT) is constructed from 12 close-up photos of various materials and participants were to choose the best SSW out of 8 choices to describe surface texture in the images in Japanese. All 102 participants seen in Juntendo University Hospital from January to August 2023 had a diagnosis of possible iNPH (age mean 77.9, SD 6.7). The answers were scored on a comprehensive scale of 0 to 1. Neuropsychological assessments included MMSE, FAB, and the Rey Auditory Verbal Learning Test (RAVLT), Pegboard Test, and Stroop Test from the EU-iNPH Grading Scale (GS). In study 1 the correlation between SSWTRT and the neuropsychological tests were analyzed. In study 2, participants were divided into two groups: the Normal Cognition group (Group A, n = 37) with MMSE scores of 28 points or above, and the Mild Cognitive Impairment group (Group B, n = 50) with scores ranging from 22 to 27 points, and its predictability were analyzed. Results: In study 1, the total SSWTRT score had a moderate correlation with the neuropsychological test results. In study 2, there were significant differences in the SSWTRT scores between groups A and B. ROC analysis results showed that the SSWTR test was able to predict the difference between the normal and mildly impaired cognition groups. Conclusion: The developed SSWTRT reflects the assessment results of neuropsychological tests in cognitive deterioration and was able to detect early cognitive deficits. This test not only relates to visual perception but is likely to have an association with verbal fluency and memory ability, which are frontal lobe functions.

Expression of IGF1R is associated with tumor differentiation and survival in patients with lung adenocarcinoma.

PURPOSE: The insulin-like growth factor 1 receptor (IGF1R) is widely expressed in normal tissues and many malignancies in humans. We investigated the clinical significance of the expression of the IGF1R gene in human lung adenocarcinoma. METHODS: A total of 238 patients with lung adenocarcinoma were investigated. Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) assays were performed to evaluate the gene expression of IGF1R, and immunohistochemical staining was done to evaluate the protein expression of IGF1R. RESULTS: Among the 238 patients with lung adenocarcinoma, 107 tumors (45.0%) were IGF1R-low and 131 tumors (55.0%) were IGF1R-high. The IGF1R gene expression ratio was significantly lower in moderately to poorly differentiated adenocarcinomas than in well-differentiated adenocarcinomas (P = 0.0388). Gene expression of IGF1R was significantly correlated with protein expression of IGF1R (r = 0.7163, P < 0.0001). Regarding patient survival, overall survival was significantly lower in patients with IGF1R-low tumors than in those with IGF1R-high tumors (63.2% versus 76.1% 5-year survival, P = 0.0188). Multivariate analysis using a Cox proportional-hazards model demonstrated that IGF1R gene status was a significant prognostic factor predicting overall survival of patients with lung adenocarcinoma (hazard ratio 1.800; P = 0.0321). Moreover, the disease-free survival rate was significantly lower in patients with IGF1R-low tumors than in those with IGF1R-high tumors (49.2% versus 64.6% 5-year survival, P = 0.0084). CONCLUSION: The present study suggests the level of IGF1R expression to be a useful prognostic marker for patients with dedifferentiated lung adenocarcinoma.

Impact of KRAS and EGFR gene mutations on recurrence and survival in patients with surgically resected lung adenocarcinomas.

BACKGROUND: Oncogenic gene mutations observed in lung adenocarcinomas, such as epidermal growth factor receptor (EGFR) and KRAS, have some predictive value for chemotherapeutic drugs or EGFR-tyrosine kinase inhibitors. However, the influence of these gene alterations on patients' prognosis remains controversial. METHODS: We retrospectively analyzed the tumors of 180 patients with completely resected pathological stage I-III lung adenocarcinoma which harbored either KRAS codon 12 mutation or EGFR gene mutations within exons 18-21 to investigate the impact of these gene mutations on the patients' survival. Gene mutations were detected by established methods. RESULTS: Of 180 patients, 32 had KRAS codon 12 mutations (KRAS group), 148 had EGFR mutations within exon 18-21 (EGFR group). Pathological stage and operation mode were independent factors for disease-free survival. However, the EGFR group had better overall survival than the KRAS group (P = 0.0271). Cox proportional hazard model revealed pathological stage (P = 0.0001) and presence of EGFR gene mutations (P = 0.0408) were independent factors for overall survival. In survival after tumor recurrence, the EGFR group had a better median survival time (46.7 months) after recurrence than the KRAS group (26.0 months). CONCLUSIONS: In patients with completely resected lung adenocarcinomas, KRAS and EGFR gene mutation status of tumors was not associated with disease-free survival. However, the presence of an EGFR gene mutation boded well for the patient's overall survival, and thus patients with EGFR mutations have a better prognosis than those with KRAS mutations.

Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma.

BACKGROUND: Patients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma. METHODS: We retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018 at our institution for information on the recurrence of the disease. RESULTS: Per the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42-36.2, P = 0.0012; and OR: 4.50, 95% CI: 1.52-13.4, P = 0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08-42.5, P = 0.0003). CONCLUSIONS: The presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.

Multiple-turnover single nucleotide primer extension reactions to detect 8-oxo-2'-deoxyguanosine in DNA.

The identification of the position of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is important to clarify the pathogenesis of many diseases. We herein developed a purine-1,3-diazaphenoxazine triphosphate (dPdapTP) and described the first example of detecting the presence of 8-oxo-dG by amplifying it several hundred times after the multiple-turnover single nucleotide primer extension reactions.

Cholesterol Crystals in the Retrieved Thrombus by Mechanical Thrombectomy for Cerebral Embolism: A Case Report and Literature Review.

There are only a few case reports in which cholesterol crystals were found in the thrombus retrieved by mechanical thrombectomy for cryptogenic stroke, leading to a definitive diagnosis. We herein report a case of aortogenic embolic stroke diagnosed by the presence of rich cholesterol crystals in the retrieved thrombus and review the previously reported cases. A woman in her 80s was transferred as an emergency due to consciousness disturbance, right conjugate deviation, and severe left hemiparesis. Magnetic resonance imaging showed occlusion of the right middle cerebral artery (MCA) and acute infarction in the territory. The MCA was recanalized by thrombectomy using an aspiration catheter and stent retriever, and the symptoms improved. Although the physiological examination did not detect the embolic source during hospitalization, pathological examination of the thrombus revealed atheroma with numerous cholesterol crystal clefts and intermixing of fibrin. Contrast-enhanced computed tomography performed based on the pathological results showed atheromatous lesions in the aortic arch as the embolic source. As a subsequent treatment, medications of a strong statin and an antiplatelet agent were continued, and the patient had no recurrence. The finding that the retrieved thrombus is a simple atheroma containing cholesterol crystals with poor hemocytes suggests embolism due to plaque rupture. Pathological examination of the thrombus obtained by thrombectomy is one of the useful diagnostic approaches for stroke etiology and the determination of its treatment.

Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma: a multi-institutional retrospective study.

OBJECTIVES: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS. CONCLUSIONS: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene.

BACKGROUND: A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has recently been identified in nonsmall-cell lung cancers (NSCLCs). We screened for EML4-ALK fusion genes and examined the clinicopathological and genetic characteristics of fusion-harboring NSCLC tumors. METHODS: We examined 313 NSCLC samples from patients who underwent resection at our hospital between May 2001 and July 2005. We screened for the fusion genes using reverse-transcription polymerase chain reaction (RT-PCR) assay and confirmed the results with direct sequencing. We also examined mutations in the epidermal growth factor receptor (EGFR), KRAS, and ERBB2 genes. RESULTS: Five EML4-ALK fusion genes were detected (four from 111 female samples and one from 202 male samples; 1.6% overall). All five genes were found in adenocarcinomas and accounted for 2.4% of the 211 adenocarcinoma samples. One EML4-ALK fusion was variant 1, and two were variant 3. In addition, we also found two new fusion variants. Patients with fusion-positive tumors were nonsmokers or light smokers. Among the 211 adenocarcinomas, mutations in EGFR, KRAS, and ERBB2 were detected in 105, 29, and 7 tumors, respectively. Interestingly, all of the fusion-positive NSCLCs had no mutations within these genes. CONCLUSIONS: EML4-ALK fusion genes were observed predominantly in adenocarcinomas, in female or nonsmoking populations. Additionally, the EML4-ALK fusions were mutually exclusive with mutations in the EGFR, KRAS, and ERBB2 genes.

Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer.

BACKGROUND: Mutations in Kelch-like ECH-associated protein 1 (Keap1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keap1 gene mutations on survival and disease-free interval using resected primary NSCLC tissue. METHODS: We retrospectively analyzed the tumors from 79 patients with completely resected pathological Stage I-II NSCLC for the presence of Keap1 gene mutations and examined the prognosis of the patients. RESULTS: Keap1 gene mutations were detected in four patients (5.1%). The postoperative 5-year survival rate for patients with Keap1 mutations was significantly lower than those without a mutation (25% vs. 76%, P = 0.038). The postoperative 5-year disease-free survival rate for patients with a mutant Keap1 tumor was slightly lower than for patients with Keap1 wild-type tumors (25% vs. 66%, P = 0.057). CONCLUSIONS: Keap1 gene mutations are likely to be associated with a worse prognosis and lower postoperative disease-free survival rates in pathological Stage I-II NSCLC.

Repeat resection of pulmonary metastasis is beneficial for patients with colorectal carcinoma.

BACKGROUND: The role for repeat pulmonary metastasectomy for colorectal carcinoma has not been well defined. To identify the class of patients who benefit from pulmonary resection of recurrent pulmonary metastases, we herein reviewed our institutional experience. METHODS: Between 1990 and 2007, 84 patients with pulmonary metastases from colorectal carcinomas underwent complete pulmonary resection, and 22 of them (26%) later underwent complete resection for repeat pulmonary metastasis. Various perioperative variables were investigated retrospectively in these patients to confirm a role for repeat metastasectomy and analyze prognostic factors after repeat pulmonary metastasectomy. RESULTS: Overall survival and disease-free survival after repeat pulmonary metastasectomy were, respectively, 61 and 32% at 5 years. On univariate analysis, male gender and less than 1 year of disease-free status after the first pulmonary metastasectomy demonstrated significantly adverse overall survival (p = 0.01 and p = 0.009, respectively). Elevated preoperative serum carcinoembryonic antigen (CEA) level and maximum tumor size larger than 3 cm were also significantly adverse prognostic factors for disease-free survival (p = 0.03 and p = 0.04, respectively). The overall survival curve after repeat pulmonary metastasectomy was almost identical with that after complete resection of the first pulmonary metastasis. CONCLUSIONS: Patients with more than 1 year of disease-free status after the first pulmonary metastasectomy demonstrated a significantly better overall survival. Normal preoperative serum CEA level and maximum tumor size <3 cm were significantly adverse prognostic factors for disease-free survival. Our data imply that repeat pulmonary metastasectomy might be beneficial as it can salvage a subset of patients with colorectal carcinoma who retain favorable prognostic determinants.

Age-related changes in the trachea in healthy adults.

To investigate age-related changes in the shape of trachea, normal male volunteers (n = 83, mean +/- SD: 47.7 +/- 20.2 years old) underwent inspiratory CT scans at full inspiration and lung function tests. Subjects who showed VC < 80% predicted or FEV1 < 80% predicted on lung function tests were excluded. The CT data, which is located at 2.0 cm above the aortic arch, were transferred to a personal computer. The tracheal area (St) and two parameters, Tracheal index (Ti) and Circularity (Ci) indicating the shape of the trachea, were automatically calculated. Ti was defined the ratio of the coronal to the sagittal diameter of the trachea, and the Ci (Ci = 4piS/L2, S: tracheal area, L: tracheal perimeter) was used to indicate the roundness of the trachea. A Ci value of less than 1 indicated the distortion of the roundness. Both St and St/BSA (body surface area) showed a significant correlation with age (r = 0.37, r = 0.52; p = 0.0006, p < 0.0001). Ti was not correlated with age (r = -0.20; p = 0.0697), whereas Ci was significantly correlated with age (r = -0.32; p = 0.00364). There were measurable age related changes of the trachea both in the area and the shape. Aging results in the increased tracheal area and a distortion of the roundness.

Octreotide, a somatostatin analogue, in the treatment of chylothorax associated with idiopathic fibrosing mediastinitis.

Fibrosing mediastinitis (FM) is a rare benign disorder that is characterized by excessive fibrotic reactions in the mediastinum. FM is associated with various diseases, including Histoplasma capsulatum infection and IgG4-related disease, and may compromise the airways, great vessels, and other mediastinal structures. Chylothorax is not a common manifestation of FM, and there is no standard treatment for FM or chylothorax. Recently, however, somatostatin and octreotide, a somatostatin analogue, were successfully used for the treatment of chylothorax due to various causes, and they are considered as putative therapeutic interventions for chylothorax. Here, we present a 28-year-old Japanese man with chylothorax due to idiopathic FM, who was successfully treated with octreotide. The patient visited our hospital because of dyspnea on exertion. On admission, chest computed tomography revealed pericardial effusion, bilateral pleural effusion, and a mass in the mediastinum. The right pleural effusion appeared chylous, with the triglyceride level of 253 mg/dl. The biopsy specimen from the mediastinal mass showed collagenous fibers and fibroblasts with moderate infiltration of lymphocytes. Neither fungi nor bacteria were cultured from the biopsy specimen. Steroid therapy was not effective. The patient was then treated with subcutaneous octreotide (100 microg three times daily). Five days after starting the treatment, the drained pleural fluid was decreased to approximately 150 ml/day from approximately 1,000 ml/day. The mediastinal mass decreased in size 2 weeks after the initiation of octreotide treatment. After discharge, the patient has received octreotide treatment for 6 months without serious adverse events. We suggest octreotide as a treatment option for FM.