Anatomy of the larynx and pharynx: effects of age,gender and height revealed by multidetector computed tomography

Although oropharyngeal and laryngeal structures are essential for swallowing, the three‐dimensional (3D) anatomy is not well understood, due in part to limitations of available measuring techniques. This study uses 3D images acquired by 320‐row area detector computed tomography (‘320‐ADCT’), to measure the pharynx and larynx and to investigate the effects of age, gender and height. Fifty‐four healthy volunteers (30 male, 24 female, 23–77 years) underwent one single‐phase volume scan (0·35 s) with 320‐ADCT during resting tidal breathing. Six measurements of the pharynx and two of larynx were performed. Bivariate statistical methods were used to analyse the effects of gender, age and height on these measurements. Length and volume were significantly larger for men than for women for every measurement (P < 0·05) and increased with height (P < 0·05). Multiple regression analysis was performed to understand the interactions of gender, height and age. Gender, height and age each had significant effects on certain values. The volume of the larynx and hypopharynx was significantly affected by height and age. The length of pharynx was associated with gender and age. Length of the vocal folds and distance from the valleculae to the vocal folds were significantly affected by gender (P < 0·05). These results suggest that age, gender and height have independent and interacting effects on the morphology of the pharynx and larynx. Three‐dimensional imaging and morphometrics using 320‐ADCT are powerful tools for efficiently and reliably observing and measuring the pharynx and larynx.     

Sex hormone and gender difference--role of testosterone on male predominance in Brugada syndrome

Introduction: The clinical phenotype is 8 to 10 times more prevalent in males than in females in patients with Brugada syndrome. Brugada syndrome has been reported to be thinner than asymptomatic normal controls. We tested the hypothesis that higher testosterone level associated with lower visceral fat may relate to Brugada phenotype and male predominance.
Methods and Results: We measured body-mass index (BMI), body fat percentage (BF%), and several hormonal levels, including testosterone, in 48 Brugada males and compared with those in 96 age-matched control males. Brugada males had significantly higher testosterone (631 ± 176 vs 537 ± 158 ng/dL; P = 0.002), serum sodium, potassium, and chloride levels than those in control males by univariate analysis, and even after adjusting for age, exercise, stress, smoking, and medication of hypertension, diabetes, and hyperlipidemia, whereas there were no significant differences in other sex and thyroid hormonal levels. Brugada males had significantly lower BMI (22.1 ± 2.9 vs 24.6 ± 2.6 kg/m²; P < 0.001) and BF% (19.6 ± 4.9 vs 23.1 ± 4.7%; P < 0.001) than control males. Testosterone level was inversely correlated with BMI and BF% in both groups, even after adjusting for the confounding variables. Conditional logistic regression models analysis showed significant positive and inverse association between Brugada syndrome and hypertestosteronemia (OR:3.11, 95%CI:1.22–7.93, P = 0.017) and BMI (OR:0.72, 95%CI:0.61–0.85, P < 0.001), respectively.
Conclusions: Higher testosterone level associated with lower visceral fat may have a significant role in the Brugada phenotype and male predominance in Brugada syndrome.     

Serologically HLA-DR—Mismatched Unrelated Donors Might Provide a Valuable Alternative in Allogeneic Transplantation: Experience from a Single Japanese Institution

To clarify the clinical significance of a serologic HLA-DR mismatch after unrelated-donor transplantation, we evaluated for hematologic malignancies 123 cases of unrelated bone marrow transplantation carried out in a single institution between 1995 and 2004. Of the patients in these cases, 12 were serologically mismatched at the single HLA-DR locus. Eighty-two patients who received HLA-matched transplantations were used as controls. Conditioning consisted of a conventional total body irradiation-based regimen or a fludarabine-based reduced-intensity regimen. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus plus short-term methotrexate. Graft failure did not develop. With a median follow-up of 42 months (range, 11-99 months), rates of overall survival, nonrelapse mortality, and relapse at 4 years were 63%, 38%, and 0%, respectively, all of which were comparable with those after HLA-matched transplantation. The frequency of acute GVHD of grades II to IV was 75%, significantly higher than after HLA-matched transplantation (42%, P = .046), and there was a trend toward an increased incidence of acute GVHD of grades III to IV after serologically HLA-DR-mismatched unrelated transplantation (27% versus 10%, P = .093). Chronic GVHD developed in 4 of 11 evaluable patients, an incidence comparable with that after HLA-matched transplantation. In summary, serologically HLA-DR-mismatched unrelated transplantation is feasible and might be an acceptable alternative for the Japanese population, although the higher incidence of acute GVHD is notable.     

Characterization of peripheral blood progenitor cells (PBPC) mobilized by filgrastim (rHuG-CSF) in normal volunteers: dose–effect relationship for filgrastim with the character of mobilized PBPC

Filgrastim (rHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) in healthy Japanese volunteers were characterized in detail using two clonal cell culture systems and double-colour flow cytometry to detect multilineage colony-forming cells and subsets of CD34⁺ cells. The kinetics of PBPC during the administration of filgrastim was studied, and possible differences in the character of progenitor cells relative to given doses of filgrastim were investigated. Filgrastim was administered subcutaneously to normal volunteers for 7 d at doses of 100, 200 or 400 μg/m² (10 per cohort). Treatment with 100 or 200 μg/m² filgrastim was well tolerated; however, the 400 μg/m² dose level was not completed because of bone pain and myalgia. The treatment strikingly mobilized various types of progenitor cells, including highly proliferative megakaryocytic colony-forming cells. The number of progenitor cells peaked on days 5 and 6. The fold increase of circulating progenitor cells from the baseline value in the volunteers treated with 200 μg/m² filgrastim was more pronounced than in those treated with 100 μg/m². Treatment with 200 μg/m² also released the less mature progenitor cells (i.e. mixed colony-forming cells, CD34⁺/33⁻ cells, and CD34⁺/HLA-DR⁻ cells) into circulation better than the 100 μg/m² dose. These results suggest that daily subcutaneous injection with 200 μg/m² filgrastim for 5 d will effectively mobilize, both qualitatively and quantitatively, PBPC in healthy donors.     

Allogeneic stem cell transplantation with fludarabine/melphalan (non-TBI and non-BU/CY) for patients aged 50 or more

Since 1999, we started to modify the conditioning regimen in allogeneic stem cell transplantation for middle-aged to elderly patients (> = 50), and experimented with 3 conditioning regimens. The clinical outcome was compared between fludarabine/melphalan (FLU/MEL) conditioning and two other conditioning regimens (reduced TBI (7.5 Gy) and BU/CY). From 1999 through 2005, a total of 33 patients aged 50 or more with a hematological malignancy received allogeneic transplantation in our institute. Seventeen received FLU/MEL conditioning and 16 received the other conditioning regimens. The FLU/MEL group included more patients receiving unrelated bone marrow transplantation. There were no differences in primary disease, risk, HLA disparity, GVHD prophylaxis and stem cell source. Sustained engraftment was achieved in all evaluable patients in both groups. Regimen-related toxicities were the same in both groups. Transplant-related-mortality (TRM), relapse rate and disease-free survival were 22% and 25%, 25% and 47%, 59% and 37% in the FLU/MEL group and in the other group, respectively. The incidence of grade II-IV acute GVHD was 25% and 13%, respectively, and that of chronic GVHD was 38% and 56%, respectively. FLU/MEL conditioning achieved satisfactory engraftment. Although the relapse rate showed a lower tendency with FLU/MEL conditioning, there were no differences as far as TRM was concerned. FLU/MEL conditioning could be a novel conditioning regimen for middle-aged to elderly patients.     

Esophageal small cell carcinoma effectively treated by cisplatin and irinotecan

Small cell carcinoma of the esophagus (SSCE) is regarded as a relatively uncommon neoplasm. Because of its aggressive characteristics with early systemic dissemination and widespread metastasis, SCCE is often associated with a poor prognosis. We report a case of carcinoembryonic antigen-positive SCCE coexistent with squamous cell carcinoma, which was successfully treated with cisplatin (CDDP) and irinotecan (CPT-11). The present case showed no evidence of distant metastasis at the time of preoperative examination. Therefore, the surgical resection was selected as a primary treatment followed by adjuvant therapy (CDDP and 5-flourouracil). However, multiple liver metastases appeared 8 months after the surgery. We changed the chemotherapy to CPT-11 and CDDP, because the regimen is effective for small cell carcinoma of the lung. After six courses of this regimen, the metastatic lesions had dramatically disappeared. These facts suggest that surgical intervention followed by a new regimen consisting of CDDP and CPT-11 is an effective treatment for SCCE.     

Reassessment of clinical implication of pretransplant surgical procedures for pulmonary invasive fungal lesions

Dealing with the recent series of allogeneic hematopoietic stem cell transplantation (allo‐SCT) performed this decade, we reassessed the clinical impact of pretransplant surgical procedures (SP) for pulmonary lesions of invasive fungal disease (IFD) on subsequent transplant outcome. We focused on the clinical outcomes of seven patients with pulmonary IFD who underwent segmentectomy (n = 4), lobectomy (n = 2) or abscess incision with drainage only (n = 1), and compared results to those of 21 patients carrying pulmonary IFD who never underwent invasive SP before allo‐SCT. The rate of exacerbation of pulmonary lesions by 180 days after allo‐SCT did not differ significantly between groups (32.2% vs 42.9%, P = 0.69). Moreover, no significant differences in non‐relapse mortality (46.4% vs 42.3%, P = 0.93) or overall survival (53.6% vs 30.9%, P = 0.45) at 1 year were evident between groups. These results indicate that pretransplant SP for pulmonary lesions might have no survival benefit under the current antifungal prophylaxis or treatment modality.