Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease.

Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years) with stage 3-5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height²). An LTI of less than 10% of the normal value (low LTI) indicates muscle wasting. Patients with low LTI (n = 40) tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3-5 CKD.

Borneol Dehydrogenase from Pseudomonas sp. Strain TCU-HL1 Catalyzes the Oxidation of (+)-Borneol and Its Isomers to Camphor.

Most plant-produced monoterpenes can be degraded by soil microorganisms. Borneol is a plant terpene that is widely used in traditional Chinese medicine. Neither microbial borneol dehydrogenase (BDH) nor a microbial borneol degradation pathway has been reported previously. One borneol-degrading strain, Pseudomonas sp. strain TCU-HL1, was isolated by our group. Its genome was sequenced and annotated. The genome of TCU-HL1 consists of a 6.2-Mbp circular chromosome and one circular plasmid, pTHL1 (12.6 kbp). Our results suggest that borneol is first converted into camphor by BDH in TCU-HL1 and is further decomposed through a camphor degradation pathway. The recombinant BDH was produced in the form of inclusion bodies. The apparent Km values of refolded recombinant BDH for (+)-borneol and (-)-borneol were 0.20 ± 0.01 and 0.16 ± 0.01 mM, respectively, and the kcat values for (+)-borneol and (-)-borneol were 0.75 ± 0.01 and 0.53 ± 0.01 s-1, respectively. Two plant BDH genes have been reported previously. The kcat and kcat/Km values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. IMPORTANCE: The degradation of borneol in a soil microorganism through a camphor degradation pathway is reported in this study. We also report a microbial borneol dehydrogenase. The kcat and kcat/Km values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. The indigenous borneol- and camphor-degrading strain isolated, Pseudomonas sp. strain TCU-HL1, reminds us of the time 100 years ago when Taiwan was the major producer of natural camphor in the world.

Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma.

BACKGROUND: Risks of perineural invasion (PNI) in T1-2 oral tongue squamous cell carcinoma (SCC) have not been specifically elucidated. METHODS: Pathological features, including PNI, were re-reviewed under regular hematoxylin-eosin staining in 190 patients with T1-2 oral tongue SCC. RESULTS: Tumor thickness >5 mm, PNI(+), and lymphovascular invasion (+) independently predicted lymph node involvement. PNI(+) and neck observation also independently predicted neck recurrence, but only PNI(+) was associated with a poor disease-specific survival (DSS; p = .003). In patients who were clinically node negative (cN0), elective neck dissection contributed to a better DSS in patients with PNI(+) tumors (p = .046), but not in patients with PNI (-) tumors (p = .809). Additionally, increased tumor thickness predicted the presence of PNI. CONCLUSION: PNI is a crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection should be performed in patients who were cN0 with PNI. Careful evaluation for PNI should be advocated in regular pathological diagnosis.

Office-based treatment of vocal fold polyp with flexible laryngosvideostroboscopic surgery.

OBJECTIVES: To evaluate the usefulness and safety of flexible laryngovideostroboscopic (FLVS) surgery in patients with vocal fold polyp and to discuss its advantages and limitations in comparison with traditional direct microlaryngoscopic technique under general anesthesia. DESIGN: Retrospective analysis. PATIENTS AND METHODS: Twenty patients with vocal fold polyp treated by FLVS surgery under topical anesthesia were reviewed. The results were evaluated by videostroboscopy and grade of the severity of dysphonia, roughness, and breathiness (GRB) scales. Phonatory results, including maximum phonation time, jitter, shimmer, and noise to harmonic ratio, were also reviewed for objective evaluations. RESULTS: All patients completed the surgery smoothly, and seven of them had a higher risk for general anesthesia because of their medical diseases. The procedure was typically accomplished within 20 minutes, and no complications were noted. Videostroboscopy showed improved degree of glottic closure (p < .001), regularity (p = .046), phase symmetry (p = .008), and mucosal wave (p = .008) after FLVS. A significant improvement was noted between preoperative and postoperative results with regard to GRB scale (p < .001, p = .001, and p = .013, respectively). Maximum phonation time also increased significantly after surgery (p = .002). Trivial mucosal residual was noted in one patient. No recurrence was found after a 6-month follow-up period. CONCLUSIONS: FLVS surgery is a highly applicable procedure with low invasiveness and minimal morbidity. It offers a simple and cost-effective alternative to the traditional direct microlaryngoscopic procedure, especially for those who are not candidates for general anesthesia or suspension of the larynx.

Different patterns of second primary malignancy in patients with squamous cell carcinoma of larynx and hypopharynx.

PURPOSE: The aim of the present study was to compare the incidence, patterns, and survival of second primary malignancy (SPM) in patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HPSCC). METHODS: We retrospectively review the medical record of 581 previously untreated patients with LSCC (392 cases) and HPSCC (189 cases) who received primary surgery with or without postoperative radiotherapy from 1990 to 2000. Data including age, sex, risk factors, subsites and TNM stage of primary tumor, treatment, site and incidence of SPM, and prognosis were collected from medical charts. RESULTS: Groups with HPSCC had a higher incidence (4.2% vs 2.9% annual rate) and shorter median time (30 vs 59 months) developing SPM rather than LSCC. Fifty-five percent of the SPM occurred in the respiratory axis in LSCC, and 66% developed in the digestive axis in HPSCC. The factors influencing the appearance of SPM included early T stage, tobacco use, and less tumor recurrence. Long-term survival was poorer in those with than without SPM (38% vs 49% at 10 years). CONCLUSIONS: There is a tendency for SPM to occur in the respiratory axis (lung and larynx) in LSCC and in the digestive axis (oral cavity, pharynx, and esophagus) in HPSCC. This information is important for posttreatment follow-up.

Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study.

PURPOSE: The efficacy and safety of gemcitabine in combination with cisplatin (GC) as the first-line treatment in patients with recurrent/metastatic (R/M) squamous cell carcinoma of head and neck (SCCHN) was examined. PATIENTS AND METHODS: Patients with R/M SCCHN without prior treatment for their R/M disease were eligible and treated with gemcitabine 1,250 mg/m(2) on day 1, day 8 and cisplatin 80 mg/m(2) on day 8 every 21 days. RESULTS: Forty patients were enrolled from March 2004 to January 2006, and 30 were evaluable for treatment effectiveness and outcome. The median age of evaluable patients was 50 years and all patients were male. Partial response was observed in 9 (30%) and stable disease in 7 (23.3%) patients. The overall response rate and disease control rate was 30 and 53.3%, respectively. The major toxic effects were ≥grade 3 leukopenia and anemia (65 and 27.5%, respectively). With a follow-up of 72 months, the median time to progression (TTP) was 128 days (95% CI, 78-242) and median overall survival (OS) was 401 days (95% CI, 216 approximately not reached). CONCLUSIONS: This GC regimen demonstrates a good activity and a promising survival period in patients with R/M SCCHN.

Positron emission tomography in surveillance of head and neck squamous cell carcinoma after definitive chemoradiotherapy.

BACKGROUND: We assessed the role of (18)F-fluoro-deoxy-glucose positron emission tomography (PET) in detecting head and neck squamous cell carcinoma (HNSCC) after definitive chemoradiotherapy (CRT). METHODS: A prospective study presented 80 PET before and after CRT for 44 patients, including 44 first-time post-CRT scans performed between 12 and 17 weeks after radiotherapy completion, as well as 10 repeated scans in the subsequent follow-up. PET interpretations were compared with clinicopathologic outcomes. RESULTS: PET demonstrated better performance than CT in post-CRT surveillance. Considering all 54 post-CRT PET scans, sensitivity for detecting primary tumors was 100%, specificity 93%, positive predictive value (PPV) 80%, and negative predictive value (NPV) 100%. For cervical diseases, sensitivity was 100%, specificity 98%, PPV 92%, and NPV 100%. For distant metastases, sensitivity was 100%, specificity 98%, PPV 86%, and NPV 100%. CONCLUSIONS: Negative PET readings were reliable for predicting free of HNSCC and helpful for selected patients in post-CRT surveillance.

Role of chest computed tomography in head and neck cancer.

OBJECTIVES: To evaluate the role of chest computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to determine the optimal timing and predictive factors for positive findings. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Two hundred seventy screening chest CT scans performed in 192 patients with HNSCC during a 42-month period were reviewed. MAIN OUTCOME MEASURES: The scans were categorized as new cases, follow-up cases, or recurrent cases. The results were classified as abnormal or normal. Scans of patients having a radiologic diagnosis of a malignant neoplasm of the lung or an indeterminate lesion were considered abnormal. Factors correlating with an abnormal chest CT scan or development of malignant neoplasm of the lung were analyzed, including the timing of imaging and the patients' clinicopathologic data. RESULTS: Seventy-nine scans (29.3%) were considered abnormal. The rate of an abnormal scan was significantly higher in the follow-up case group (44.2%) than in the new case group (14.2%) (P < .001). Ten of 15 indeterminate scans (66.7%) with small (<1 cm) solitary pulmonary nodules showed disease progression on subsequent follow-up scans, changing the patients' diagnoses to a malignant neoplasm of the lung. The predictive factors for development of a malignant neoplasm of the lung were initial N2 or N3 disease, stage IV disease, recurrent disease, and distant metastasis to another site. CONCLUSIONS: Chest CT is recommended for high-risk patients, especially during the follow-up period. Intensified evaluation and management are mandatory for indeterminate small solitary pulmonary nodules because of the high rate of malignant neoplasms.

Chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer.

OBJECTIVE: Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. METHODS: The study population consisted of 42 consecutive patients with resectable stage III-IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). RESULTS: Grade 3-4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P < 0.001 and = 0.003), overall survival (OS) (P < 0.001 and = 0.004) and laryngeal preservation survival (LPS) (P = 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. CONCLUSIONS: Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.

Methotrexate and leucovorin double-modulated 5-fluorouracil combined with cisplatin (MPFL) in metastatic/recurrent head and neck cancer.

BACKGROUND: To determine the efficacy and safety profile of the combination of cisplatin and 5-fluorouracil modulated both by methotrexate and leucovorin in metastatic/recurrent squamous cell carcinoma of the head and neck. METHODS: Twenty-eight patients were treated with cisplatin 40 mg/m2/day continuous infusion for 24 hours on day 1; high-dose 5-fluorouracil 2,000 mg/m2/day and leucovorin 100 mg/m2/day continuous infusion for 48 hours on days 1 and 2; methotrexate 40 mg/m2/day as a bolus infusion 4 hours before 5-fluorouracil and leucovorin on day 1. The treatment was repeated every 2 weeks in a cycle. RESULTS: The overall response rate was 25%, and 14% of the patients achieved stable disease status. Subgroup analysis demonstrated significantly improved overall survival in the disease-control group (12.0 months vs. 5.3 months, p<0.001). Only 3 (10.7%) patients developed grade 3-4 neutropenia, and none developed grade 3-4 non-hematologic toxicity. CONCLUSION: This multiagent-containing regimen has an excellent safety profile and improved survival in disease-control group of patients with metastatic/recurrent squamous cell carcinoma of the head and neck.

Effectiveness of pharmacokinetic modulating chemotherapy combined with cisplatin as induction chemotherapy in resectable locally advanced head and neck cancer: phase II study.

PURPOSE: To test the efficacy and safety of pharmacokinetic modulating chemotherapy combined with cisplatin (PMC-cisplatin) as induction chemotherapy (ICT) before definitive treatment in patients with respectable locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Patients with stage III-IV resectable locally advanced HNSCC were enrolled. All eligible patients received PMC-cisplatin regimen as ICT containing intravenous leucovorin 250 mg/m(2) and 5-FU 600 mg/m(2) on day 1, oral tegafur-uracil (UFUR) 250 mg/m(2)/day on days 1-5, repeated every week for six courses. Cisplatin 100 mg/m(2 )was given during the first and fourth courses of PMC. For ICT responders, concurrent chemoradiotherapy (CRT) with cisplatin/tegafur-uracil/70 Gy radiotherapy was performed. Salvage surgery plus postoperative CRT was given to ICT non-responders. RESULTS: The overall response rate of PMC-cisplatin as ICT was 76%, including a complete remission rate of 23%. The overall organ preservation rate of the multimodality treatment was 75%, with 97% in ICT responders. At a median follow-up of 25 months, 47% of the patients were still alive and disease-free. The superiority of disease-free survival was demonstrated in ICT responders. The 3-year overall survival rate was 67%. The toxicity of treatment was acceptable. CONCLUSIONS: Application of PMC-cisplatin as the induction chemotherapy before definitive treatment provides a promising result in treatment response and survival of advanced HNSCC. This regimen is effective and safe, and further studies considering the combination of PMC with other chemotherapeutics such as taxanes to improve the clinical outcome of advanced HNSCC is warranted.

Second primary malignancies in squamous cell carcinomas of the tongue and larynx: an analysis of incidence, pattern, and outcome.

BACKGROUND: Head and neck cancer patients have a higher risk of developing a second primary malignancy (SPM) than the general population. This study was conducted to identify the characteristics of SPM and its impact on survival in patients with squamous cell carcinoma of the tongue (TSCC) and larynx (LSCC). METHODS: A retrospective study was conducted of 538 patients who were treated by surgery primarily for TSCC (n = 146) and LSCC (n = 392) from 1990 to 2000. The incidence, site, and overall survival of SPMs were evaluated. RESULTS: Seventy-seven patients developed SPM during the follow-up period (median, 73 months), including 18 (12%) with TSCC and 59 (15%) with LSCC. Fifty-six percent of SPMs of the TSCC group appeared in the oral cavity. Among the SPMs of LSCC patients, 54% developed in the lung (31%) and larynx (24%). The 5-year overall survival after the diagnosis of SPM in the head and neck was 39%, compared to 29% for SPM in other areas (p = 0.010). CONCLUSION: SPMs after treatment of TSCC and LSCC are similar in incidence but distinct in pattern. SPMs within the head and neck are associated with a better prognosis than those outside this area.

Angiofibroma of the hypopharynx.

Primary extranasopharyngeal angiofibroma is very rare. To date, approximately 60 cases have been reported in the English literature. Only 1 case was confined to the posterior wall of hypopharynx. In August 2000, a 68-year-old man presented with a 6-month history of progressive foreign-body sensation in the throat and intermittent inspiratory stridor. Endoscopic examination of the larynx and pharynx revealed a nonpulsatile, pink-grayish, polypoid mass arising from the posterior pharyngeal wall of the left hypopharynx. Under general anesthesia, this tumor mass was subsequently removed by the endoscopic CO2 laser. The histologic diagnosis was an angiofibroma. Three-year follow-up found no evidence of tumor recurrence or post-operative complications.