A pilot study on intermittent every other days of 5-dose Filgrastim compared with single Pegfilgrastim in breast Cancer patients receiving adjuvant Docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy.

Aim To compare the efficacy and safety of intermittent every other days 5-dose filgrastim with single pegfilgrastim in patients with breast cancer receiving adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy. Methods In this pilot study, Korean patients who had undergone complete resection for breast cancer and scheduled for adjuvant TAC chemotherapy were enrolled. Patients were randomized to receive either intermittent 5 doses of filgrastim (5 mcg/kg/day) or once-a-cycle pegfilgrastim (6 mg) as primary prophylaxis during the first three cycles of the TAC chemotherapy. Absolute neutrophil count (ANC) was analyzed as well. Results A total of 22 patients were randomly and equally divided into filgrastim or pegfilgrastim arms. Febrile neutropenia (FN) occurred in 1 patient in the pegfilgrastim arm (1 of 33 cycles) and none in the filgrastim arm. G3 neutropenia occurred in 1 patient (1 of 33 cycles) in the filgrastim arm and 2 patients (4 of 33 cycles) in the pegfilgrastim arm (P = 0.476). G4 neutropenia occurred in 11 patients (28 of 33 cycles) in the filgrastim arm and 9 patients (18 of 33 cycles) in the pegfilgrastim arm (P = 0.476). Except for on day 9 in cycle 3, there was no significant difference between the two groups in terms of ANC. Conclusion We observed no significant differences between the two methods of prophylaxis in terms of FN and G3/4 neutropenia incidence in patients receiving adjuvant TAC chemotherapy. Intermittent every other days 5-dose filgrastim may be available alternative to pegfilgrastim.

Pretreatment depression as a prognostic indicator of survival and nutritional status in patients with head and neck cancer.

BACKGROUND: The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and <14, respectively. Univariate and multivariate analyses were performed to assess whether the presence of depression was associated with overall survival, disease-free survival (DFS), or posttreatment changes in nutritional status and laboratory data. RESULTS: Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P < .05). Depressive patients had lower pretreatment serum albumin levels than nondepressive patients (P < .05). CONCLUSIONS: There was a significant correlation between pretreatment depression and pretreatment QOL, nutritional status, and survival outcomes in patients with HNSCC.

An Introduction to a Head and Neck Cancer-Specific Frailty Index and Its Clinical Implications in Elderly Patients: A Prospective Observational Study Focusing on Respiratory and Swallowing Functions.

INTRODUCTION: Frailty refers to a decreased physiologic reserve in geriatric patients and its importance in terms of treatment planning and outcome prediction has been emphasized in oncologic practices for older patients with cancer. We investigated the clinical implications of a head and neck cancer (HNC)-specific frailty index suggested by prospective clinical and functional evaluations of HNC patients. MATERIALS AND METHODS: We analyzed data on 165 elderly patients with HNC who were prospectively enrolled in our hospital from 2010 to 2013. Pretreatment functional evaluations were performed according to all comprehensive geriatric assessment (CGA) domains. We additionally evaluated the patients' respiratory and swallowing functions using pulmonary function tests, voice handicap index (VHI), MD Anderson Dysphagia Inventory (MDADI), and other associated tests. Factors affecting the 2-year morbidity and mortality were also analyzed. RESULTS: Respiratory and swallowing problems were major causes of 2-year morbidity. Pretreatment performance status, VHI ≥8, MDADI <70, dental problems, and chemotherapy were significantly associated with early morbidity and mortality (all p < .05). CGA-assessed frailty was found in 72 patients (43.6%) and was significantly associated with 2-year mortality (p = .027) but not with morbidity (p = .716). The high-risk group according to our new HNC-specific frailty index that included functional evaluations of respiration and swallowing showed significantly higher 2-year morbidity (p = .043) and mortality (p < .001). CONCLUSION: Pretreatment functional disabilities related to respiration and swallowing were significantly associated with early morbidity and mortality. The suggested index would be more useful for assessing frailty in elderly HNC patients. IMPLICATIONS FOR PRACTICE: This study is the first report in terms of suggesting a new frailty index focusing on respiratory and swallowing functions in elderly patients with head and neck cancer. This study shows that functional disabilities associated with respiration and swallowing significantly affected early morbidity and mortality in these elderly patients. The head and neck cancer-specific frailty index described in this report, which includes functional evaluations of respiration and swallowing, significantly predicted both early morbidity and mortality.

Temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma: is there an optimal time for stent removal?

OBJECTIVE: To investigate the influence of the timing of stent removal on the outcome of temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma. METHODS: Retrospective analysis was performed on 52 patients undergoing temporary stent placement. Stents were electively removed within 4 weeks in 15 patients (group A), 4-6 weeks in 17 patients (group B) and after 6 weeks in 20 patients (group C). Recurrent symptoms after stent removal, dysphagia score and overall survival periods were compared among the groups. RESULTS: Stent placement and removal were technically successful in all patients. The dysphagia score was significantly improved in all groups (P < 0.001). In 19 patients (36 %), recurrent symptoms occurred 15-441 days after stent removal. In group A, recurrent obstruction was significantly higher than in groups B (P = 0.049) and C (P = 0.019). Incidence of oesophago-respiratory fistulas in group C was significantly higher than in group A (P = 0.027). There was no significant difference in survival periods. CONCLUSION: The ideal time for stent removal likely falls between 4 and 6 weeks following the start of palliative CCRT allowing the temporary stents to relieve dysphagia effectively in patients with unresectable oesophageal carcinoma. KEY POINTS: • Stents are usually required for unresectable oesophageal carcinoma • Optimal timing of stent removal is 4-6 weeks after starting palliative CCRT. • Early stent removal (<4 weeks) is associated with higher recurrence rates. • Delayed stent removal (>6 weeks) is associated with greater oesophago-respiratory fistula development.

A bioluminescent assay system for whole-cell determination of hormones.

A bioluminescent-assay system was fabricated for an efficient determination of bioactive small molecules in physiological samples. The following three components were newly created for this assay system: (i) a single-chain probe exerting a 7.2-times stronger optical intensity than conventional ones, (ii) a high throughput assay device uniquely designed for the assay system with ca. one-fourth smaller standard deviation (S.D.) to samples than without the device, (iii) a buffer cocktail optimized for the assay system. The advantages of the assay system were evaluated by determining (i) the stress hormone levels in human saliva and (ii) multicolor imaging of genomic and nongenomic effects of woman sex hormones. This study guides on how to fabricate an efficient assay system for bioactive small molecules with convenience and high precision.

Polytetrafluoroethylene-covered retrievable expandable nitinol stents for malignant esophageal obstructions: factors influencing the outcome of 270 patients.

OBJECTIVE: The purpose of this study was to evaluate the clinical effectiveness of polytetrafluoroethylene (PTFE)-covered retrievable expandable nitinol stents in patients with malignant esophageal strictures and to identify prognostic factors associated with clinical outcomes. MATERIALS AND METHODS: From 2001 to 2010, 320 PTFE-covered stents were placed in 270 patients. Technical and clinical success, complications, survival, and stent patency were measures of clinical effectiveness. The relationships among complications and age, sex, stricture location, stricture length, chemotherapy alone, chemoradiotherapy, and malignancy source were examined. Independent prognostic factors of overall survival and stent patency were identified. RESULTS: Stent placement and removal were technically successful and tolerated without procedural complications, and 98% of patients achieved clinical success. The complication rate was 30%. Two removed stents exhibited covering membrane separation. Chemotherapy was associated with increased stent migration (p = 0.002). Stricture location and chemoradiotherapy were associated with esophagorespiratory fistula development (p = 0.033 and p < 0.001, respectively). Median and mean survival periods were 114 days (95% CI, 102-126 days) and 166 days (138-193 days). Chemotherapy and chemoradiotherapy were independent prognostic factors for survival (p = 0.050 and p = 0.032, respectively). The median and mean stent patency periods were 60 days (41-79 days) and 90 days (71-108 days). Chemoradiotherapy was the only independent prognostic factor for stent patency (p = 0.012). CONCLUSION: The PTFE-covered stents were clinically effective. Membrane degradation was not evident, although 0.7% of the patients experienced covering membrane separation. Chemotherapy was associated with increased migration and prolonged survival. Chemoradiotherapy was associated with increased esophagorespiratory fistula formation and decreased stent patency.

The mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus.

Tetrandrine (TET) is a bis-benzylisoquinoline alkaloid derived from the radix of Stephania tetrandra S. Moore. TET performs a wide spectrum of biological activities. The radix of S. tetrandrae has been used traditionally in Asia, including Korea, to treat congestive circulatory disorders and inflammatory diseases. The aim of this study was to examine the mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus. The mechanism was investigated by studying the effects of TET in combination with detergent or membrane potential un-couplers. In addition, the direct involvement of peptidoglycan (PGN) was assessed in titration assays. TET activity against S. aureus was 125-250 µg/mL, and the minimum inhibitory concentration (MIC) of the two reference strains was 250 µg/mL. The OD(600) of each suspension treated with a combination of ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl) aminomethane (TRIS), and Triton X-100 (TX) with TET (0.25×MIC) had been reduced from 43% to 96%. Additional structure-function studies on the antibacterial activity of TET in combination with other agents may lead to the discovery of more effective antibacterial agents.

A bioluminescent probe for salivary cortisol.

Cortisol is a classical biomarker for the stress levels of human beings. We fabricated highly sensitive bioluminescent probes for salivary cortisol. The following strategies were contrived in the molecular design. Gaussia princeps luciferase (GLuc) was dissected into two fragments, between which an N-terminal-extended ligand binding domain of glucocorticoid receptor (GR HLBD), named Simgr4, was inserted. First, this unique single-chain probe was then situated downstream of a glucocorticoid response element (GRE) promoter in a reporter-gene system for constructing two ON-OFF switches for cortisol. Second, a circularly permutated (CP) variant of Simgr4 was formulated. The reporter-gene system exerted an improved signal-to-background (S/B) ratio of 8.5 to cortisol. Furthermore, a circularly permutated (CP) variant of Simgr4 exerted a 10× enhanced detection limit to cortisol and a long dynamic range from 10(-9) to 10(-6) M cortisol, covering all of the normal clinical ranges of serum, urine, and saliva. This optimized probe successfully determined daily fluctuations of salivary cortisol and the correlations with those by ELISA. This study is the first to investigate the contribution of the HLBD of a nuclear receptor and multiple ON-OFF switches for molecular probes and salivary cortisols.

The Association between Herpes Zoster and Increased Cancer Risk: A Nationwide Population-Based Matched Control Study.

BACKGROUND: Herpes zoster (HZ) is strongly associated with decreased immune function, a factor of cancer development. Previous studies suggested inconsistent results regarding the association between HZ and increased cancer risk. We aimed to analyze the association between HZ and specific cancer risk. METHODS: Of 134,454 patients diagnosed with HZ between 2002 and 2015, 81,993 HZ patients were matched 1:1 with non-HZ individuals by age, sex, and Charlson comorbidity index. Both groups were examined at 1, 3, and 5 years for cancer diagnosis. A Cox proportional hazard regression model was used to estimate cancer risk in both groups. The postherpetic neuralgia (PHN) and non-HZ groups were compared for specific cancer risk. RESULTS: The HZ group showed a slightly decreased overall cancer risk compared with the non-HZ group (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.97, p = 0.002). The HRs for specific cancer risk were 0.41 (95% CI, 0.33-0.50, p < 0.001); 0.86 (95% CI, 0.81-0.91, p < 0.001); 0.87 (95% CI, 0.78-0.97, p = 0.014); 0.80 (95% CI 0.73-0.87, p < 0.001); 1.20 (95% CI, 1.07-1.34, p = 0.001); and 1.66 (95% CI, 1.35-2.03, p < 0.001) for cancers of the lips, mouth, and pharynx; digestive system; respiratory system; unknown secondary and unspecified sites; thyroid and endocrine glands; and lymphoid and hematopoietic systems, respectively. The HZ with PHN group showed higher HR for specific cancer risk, such as lymphoid and hematopoietic systems (95% CI, 1.27-2.39, p < 0.001). CONCLUSION: HZ was associated with increased or decreased incidence of specific cancers. PHN further increased the risk of developing certain cancers in HZ patients.

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer.

PURPOSE: Genexol-PM is a Cremophor EL-free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Enhancement of the enzymatic digestibility of waste newspaper using Tween.

Methods of increasing the enzymatic digestibility of waste newspaper by adding Tween (TW)-20 and 80 surfactants were investigated. Tween-series surfactants were selected because these surfactants increase cellulase activity during enzymatic hydrolysis and do not inhibit cell growth in downstream fermentation processes. When surfactant was used in a pretreatment, a benefic effect was expected in the enzymatic hydrolysis stage owing to surfactant carry-over from the pretreatment stage immediately upstream of the hydrolysis. However, because it was necessary to wash the pretreated substrate with water to remove inhibitors produced during pretreatment, no added benefit was obtained. When surfactant was used in the pretreatment only, it was found that it had a marked effect on digestibility and that this effect was higher at lower enzyme loadings. Also, TW-80 was found to be more effective than TW-20, and the addition of enzyme and TW-80 to substrate at the beginning of enzyme reaction was found to most effectively increase digestibility. When TW-80 was added into either the pretreatment stage or the hydrolysis stage the digestibilities of untreated sample increased by approx 40%, whereas an increase of only 45% was observed when TW-80 was added to both stages. These results show that the addition of surfactant to either the pretreatment or the enzymatic hydrolysis stage is sufficient to increase digestibility.

A Multichannel Bioluminescence Determination Platform for Bioassays.

The present protocol introduces a multichannel bioluminescence determination platform allowing a high sample throughput determination of weak bioluminescence with reduced standard deviations. The platform is designed to carry a multichannel conveyer, an optical filter, and a mirror cap. The platform enables us to near-simultaneously determine ligands in multiple samples without the replacement of the sample tubes. Furthermore, the optical filters beneath the multichannel conveyer are designed to easily discriminate colors during assays. This optical system provides excellent time- and labor-efficiency to users during bioassays.

Diffusion of sulfuric acid within lignocellulosic biomass particles and its impact on dilute-acid pretreatment.

Intra-particle diffusion of sulfuric acid into sugarcane bagasse, corn stover, rice straw and yellow poplar was investigated to determine the effective diffusivity of sulfuric acid within the porous biomass structure. Diffusion experiments were conducted over 25-75 degrees C for two different biomass sizes using dynamic diffusion test cells. Diffusivities of sulfuric acid in agricultural residues were significantly higher than those of hard wood. Diffusivity data for each biomass were fitted into the Arrhenius equation for extrapolation to higher temperatures. The diffusivity data were subsequently incorporated into a theoretical model to determine acid profile within the biomass matrix. The modeling results indicate that intra-particle diffusion of acid influences the rate of dilute-acid pretreatment if unground biomass feedstock is used under normal pretreatment conditions. A criterion was set up to determine the critical biomass size at which the intra-particle acid diffusion becomes a rate-influencing factor for a given pretreatment condition.

Enhancement of enzymatic digestibility of recycled newspaper by addition of surfactant in ammonia-hydrogen peroxide pretreatment.

The effect of surfactant on enzymatic digestibility was investigated during the pretreatment stage. Newspaper was pretreated with an ammonia-hydrogen peroxide mixture on a shaking bath at 40 degrees C and 130 strokes/min for 3 h. Two kinds of nonionic surfactants, NP series and Tween series, were utilized. The effect of hydrophile-lipophile balance (HLB) value of both series surfactants on digestibility was found to be negligible, even though de-inking efficiency was improved as HLB value was increased. The effect of surfactant loading on digestibility was small, below 0.5 wt%, and negligible above 0.5 wt% at 60 international filter paper units (IFPU). The percentage improvement in digestibility increased as enzyme loading decreased. Digestibility of NP-5-added sample relative to control sample, increased significantly at an enzyme loading <60 IFPU, i.e., 19 and 13% at 15 and 30 IFPU, respectively. Such an increase in digestibility was not explained clearly from the experimental results. It was also found that ink removal before enzymatic hydrolysis is very important to enhance digestibility.

Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?

AIM: To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications. PATIENTS AND METHODS: The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group. RESULTS: There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups. CONCLUSION: CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.

Metastatic carcinomas to the oral cavity and oropharynx.

BACKGROUND: Metastases to the oral/oropharynx are very rare and their diagnosis is challenging. METHODS: We reviewed pathologic data for malignant tumors of the oral/oropharynx that were diagnosed at the Asan Medical Center, Seoul, Korea from 1995 until 2010. RESULTS: Twenty-nine cases of oral/oropharyngeal metastases were retrieved, comprising 2.0% of 1,445 malignancies. The most common primary sites were the liver and lung, followed by the stomach, colon, breast, prostate, and kidney. The gingiva was the most common metastatic site, followed by the tonsil/pillar, mandible, tongue, tongue base, palate mucosa, mouth floor, and buccal mucosa. Intervals between detection of primary tumors and metastases were variable, from -1 month to 104 months. Ten patients with lung (7 cases), liver, stomach, and kidney carcinomas manifested with oral/oropharyngeal metastases as the first sign of systemic metastases. The majority of patients had died within one year of the onset of an oral/oropharyngeal metastasis, but exceptionally long-lived cases were also present. The survival periods of patients with lung cancers were longer than those of patients with non-pulmonary tumors. CONCLUSIONS: An awareness of the incidence, common primary sites, metastatic subsites, and metastatic courses or patterns of oral/oropharyngeal metastases is helpful in the diagnosis of metastatic carcinomas.

Membrane degradation of covered stents in the upper gastrointestinal tract: frequency and clinical significance.

PURPOSE: To evaluate the frequency, clinical significance, and predictive factors of membrane degradation of covered stents in the upper gastrointestinal (UGI) tract. MATERIALS AND METHODS: From 1996 to 2006, 166 stents were removed from 151 patients. Indications for stent removal included temporary stent placement for esophageal cancer before radiation therapy or radiation-chemotherapy (n = 53), stent migration (n = 40), temporary stent placement for a benign UGI stricture (n = 32), pain (n = 21), recurrent obstruction (n = 16), incomplete stent expansion (n = 1), recurrent transesophageal fistula (n = 2), and aspiration (n = 1). Removed stents were examined to evaluate possible causes of membrane degradation. Multivariate analysis was performed to determine the predictive factors of membrane degradation. RESULTS: Degradation of the covering membrane occurred in 14 of the 166 stents (8%). Recurrent obstruction due to tumor ingrowth (n = 7) and reopening of the transesophageal fistula (n = 1) through the degraded membrane occurred in eight stents (5%). At multivariate logistic regression analysis, the type of covering membrane (P = .018), stricture location (P = .006), and duration of stent placement (P = .002) were significantly associated with degradation of the covering membrane. CONCLUSIONS: Degradation of the covering membrane after stent placement in the UGI tract is not an uncommon event, and recurrent obstruction or fistula can occur through the degraded membrane. A polyurethane membrane is not biostable and dissolves over time, particularly in the gastroduodenal area.

Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer.

Genexol-PM is a novel Cremophor EL-free polymeric micelle formulation of paclitaxel. This single arm, multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM in patients with histologically confirmed metastatic breast cancer (MBC). Forty-one women received Genexol-PM by intravenous infusion at 300 mg/m2 over 3 h every 3 weeks without premedication until disease progression or intolerability. A total of 331 chemotherapy cycles were administered, with a median of 8 cycles per patient (range, 1-16). Overall response rate was 58.5% (95% CI: 43.5-72.3) with 5 complete responses and 19 partial responses. Thirty-seven patients who received Genexol-PM as a first-line therapy for their metastatic disease showed a response rate of 59.5% (95% CI: 43.5-73.7), and two responses were reported in four patients treated in the second-line setting for their metastatic disease. The median time to progression (TTP) for all patients was 9.0 months (range, 1.0-17.0+ months). Grade 3 non-hematologic toxicities included sensory peripheral neuropathy (51.2%), and myalgia (2.4%). Eight patients (19.5%) experienced hypersensitivity reactions, with grade 3 in two patients. Hematologic toxicities were grade 3 and 4 neutropenia (51.2 and 17.1%, respectively), and grade 1 and 2 thrombocytopenia (22.0%). Notably, no febrile neutropenia was observed. Genexol-PM appears a promising new paclitaxel in view of significant efficacies. Further trials with different dosing schedules, durations of delivery, or in combination with other drugs are warranted.

Comparison of temporary and permanent stent placement with concurrent radiation therapy in patients with esophageal carcinoma.

PURPOSE: To assess the clinical effectiveness of temporary metallic stent placement with concurrent radiation therapy in patients with esophageal carcinoma by comparing it with permanent stent placement with concurrent radiation therapy. MATERIALS AND METHODS: Covered retrievable expandable nitinol stents were placed in 47 patients with esophageal carcinoma 1 week before starting radiation therapy; the stents were electively removed 4 weeks after placement in 24 patients (group A), while not electively removed in the other 23 patients (group B). In cases of complications, the stents were also removed from patients in groups A and B. The dysphagia score, complications (severe pain, granulation tissue formation, stent migration, esophagorespiratory fistula, and hematemesis), tumor overgrowth/regrowth, reintervention rates, and dysphagia-progression-free and overall survival rates were compared in the two groups. RESULTS: Stent placement or removal was technically successful and well tolerated in all patients. The dysphagia score was significantly improved in both groups after stent placement (P < .01). Each of the stent-related complications was less in group A than in group B but there was no significant difference. However, the total number of patients with one or more than one complications and who needed related reinterventions was significantly less in group A than in group B (P = .042 and .030, respectively). Tumor overgrowth/regrowth and the total number of patients who required related reinterventions was not significantly different (P = 1.00 and .517, respectively). Dysphagia-progression-free and overall survival rates were significantly longer in group A than in group B (P = .005 and .001, respectively). CONCLUSION: Temporary placement of a covered retrievable expandable metallic stent with concurrent radiation therapy for patients with esophageal carcinoma is beneficial for reducing complications and related reinterventions and for increasing resultant survival rates compared with permanent esophageal stent placement.

Retrievable covered nitinol stents: experiences in 108 patients with malignant esophageal strictures.

PURPOSE: The authors report their experience with three types of retrievable covered nitinol stents in patients with malignant esophageal strictures. MATERIALS AND METHODS: Three types of retrievable covered nitinol stents were designed. Type A stents were placed in 45 patients, type B stents were placed in 29 patients, and type C stents were placed in 34 patients. The stents were removed with use of a stent retrieval set under fluoroscopic guidance when the stents caused complications. Stent patency, symptom relief, survival rate, and complications were analyzed relative to stent type and radiation therapy. RESULTS: The timing of radiation and the stent type have significant effects on occurrence of complications such as stent migration and fistula formation (P =.002 and P = 0.029, respectively). Complications were significantly more frequent in patients with the type B stent than those with type A or type C stents (P =.008). Patients who underwent radiation therapy before stent placement or who underwent no radiation therapy experienced substantially less complications than those who underwent radiation therapy after stent placement (P =.005 and P <.001, respectively). The survival period was significantly longer in patients who underwent radiation therapy after stent placement than in the other groups (P =.034). Stents were removed from 15 patients (14%) 2 days to 16 weeks (mean, 4 weeks) after stent placement as a result of severe pain (n = 7), stent migration (n = 6), or stent deformity (n = 2). Stent removal was well tolerated in all patients. CONCLUSION: Use of retrievable covered nitinol stents seems to be a safe and effective method of treatment in patients with malignant esophageal strictures. However, removal of the stents was needed in 14% of the patients because of complications. Patients who underwent radiation therapy after stent placement and those with the type B stent experienced more complications than other patients.