Renal mobility during uncoached quiet respiration: an analysis of 4DCT scans

PURPOSE: Data on organ mobility is required for optimizing radiotherapy. Renal mobility was studied in four-dimensional computed tomography (4DCT) scans acquired during uncoached respiration. METHODS AND MATERIALS: The 4DCT scans of 54 patients, in whom at least the upper pole of both kidneys were visualized in all 10 respiratory phases, were analyzed. Scans were performed on a 16-slice CT scanner (slice index and reconstruction, 2.5 mm) during quiet, uncoached respiration. Mobility of the renal apex was evaluated in all patients by use of the z-position on CT slices. Reproducibility of mobility was studied in 8 patients who underwent 1 or 2 repeat 4DCT scans. RESULTS: Mobility was predominantly craniocaudal, with a mean of 9.8 mm for the left kidney and 9.0 mm for the right kidney. Large interpatient variations were observed that ranged from 2.5 to 30 mm (left) and 2.5 to 20 mm (right), and mobility of 1 kidney did not predict for mobility of the contralateral organ. Reproducibility of renal mobility and position at end-expiration was poor, with positional variations in repeat scans appearing to correlate with changes in the amplitude of respiratory waveform and total lung volume. CONCLUSIONS: Large interpatient variations in renal movement occur during uncoached respiration, which indicates that respiratory coaching is useful for 4DCT imaging and treatment delivery.     

Evolution of chronic dysphagia following treatment for head and neck cancer

We would like to assess the evolution of chronic dysphagia (1 year or more) following treatment for head and neck cancer. Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1-7. Each patient had at least 2 MBS. Severity of dysphagia was compared between the first and last MBS study to determine whether the swallowing dysfunction had returned to normal. Patients with complaint of dysphagia and normal MBS also underwent a regular barium swallow to assess the structural integrity of the pharynx and esophagus. Between 1996 and 2001, 25 patients with dysphagia underwent repeat MBS following treatment. Swallowing dysfunction did not return to normal in the majority of the patients. At a median time of 26 months following treatment (range 15-82 months), only two patient (8%) had normalization of the swallowing. The severity of dysphagia decreased in eight patients (32%), remained unchanged in 12 patients (48%), and worsened in five patients (20%). Eight patients (32%) still had aspiration problems at 12-83 months following treatment. Six patients (24%) required dilation because of pharyngeal stenosis. Three patients who required dilation had improvement of the dysphagia severity. Chronic dysphagia is a relentless process possibly due to excessive scarring. Patients with chronic dysphagia are at risk of malnutrition, and aspiration. Management of chronic dysphagia requires a team approach with nutritional support, psychological counseling, dilation, and tube feedings when indicated.     

A rare case of primary Ewings sarcoma of the nasal bone

Primary Ewing’s sarcoma of the nasal bone has not been previously described. This case presented as a mass in the left ala of the nose in a five year old female child. The clinical, radiological, microscopic features are described and a review of literature is presented. The case was treated with neoadjuvant chemotherapy and local electron beam radiation therapy. The child was free of disease when she reported for follow up in July 1997. Although wide excision is part of the treatment approach in Ewing’s sarcoma, in sites where surgery is not suitable local radiotherapy and chemotherapy adequately controls primary disease.     

Antioxidant activity and total phenolic content of ethanolic extract of Caesalpinia bonducella seeds

The aim of this study was to assess the in vitro potential of ethanolic extract of Caesalpinia bonducella seeds as a natural antioxidant. The DPPH activity of the extract (20, 40, 50, 100 and 200 μg/ml) was increased in a dose dependent manner, which was found in the range of 38.93–74.77% as compared to ascorbic acid (64.26–82.58%). The IC₅₀ values of ethanolic extract and ascorbic acid in DPPH radical scavenging assay were obtained to be 74.73 and 26.68 μg/ml, respectively. The ethanolic extract was also found to scavenge the superoxide generated by EDTA/NBT system. Measurement of total phenolic content of the ethanolic extract of C. bonducella was achieved using Folin–Ciocalteau reagent containing 62.50 mg/g of phenolic content, which was found significantly higher when compared to reference standard gallic acid. The ethanolic extract also inhibited the hydroxyl radical, nitric oxide, superoxide anions with IC₅₀ values of 109.85, 102.65 and 89.84 μg/ml, respectively. However, the IC₅₀ values for the standard ascorbic acid were noted to be 70.79, 65.98 and 36.68 μg/ml respectively. The results obtained in this study clearly indicate that C. bonducella has a significant potential to use as a natural antioxidant agent.     

Gel core liposomes: an advanced carrier for improved vaccine delivery

Many sub-unit vaccines are successful in preventing the occurrence of disease, but their use is largely restrained due to low immunogenicity. Novel carrier-based vaccine could serve as a vaccine adjuvant to overcome low immunogenicity of sub-unit vaccines. The use of liposomes as a delivery system for antigen is well recognized but they are unstable and release of antigen from them cannot be controlled over a prolonged period of time. To overcome the limitation of liposomes, this study has developed gel core liposomes in which a core of polymer was incorporated inside the liposomal vesicles, which serve the function of skeleton and provide mechanical strength to vesicles. In the present investigation BSA-loaded gel core liposomes were prepared by reverse phase evaporation method and characterized for vesicles size, shape, entrapment efficiency, in vitro release and stability studies. The in vivo studies to evaluate antigen presenting potential of the gel-core liposomes was performed in Balb/c mice by measuring the immune response elicited by intramuscular administration of BSA-loaded gel core liposomes and compared with intramuscularly administered BSA-loaded conventional liposomes, alum adsorbed BSA and plain antigen. Results indicate that intramuscular immunization with gel core liposomes induces efficient systemic antibody responses against BSA as compared to other formulations. The gel core liposomal formulation provides good entrapment efficiency, enhanced in vitro stability, prolonged antigen release and effective immunoadjuvant property, justifying its potential for improved vaccine delivery.     

What margins are necessary for incorporating mediastinal nodal mobility into involved-field radiotherapy for lung cancer?

The mobility of mediastinal nodes was studied on multiple CT scans of the thorax from patients with non-small-cell lung cancer.

A total of 10 enlarged mediastinal nodes/masses were identified in 8 patients with non-small-cell lung cancer. Nodal locations were classified using the Naruke/ATS-LCSG system, and between 3 and 6 scans were available for each site. The CT data sets were coregistered, and the contoured nodes were automatically projected onto the initial planning CT scan. An encompassing nodal volume (ENV) of all contours of a particular node was manually contoured on all scans. Individual nodal volumes were expanded in three dimensions to establish additional margins required to encompass the ENV.

The mean volume of nodes studied ranged from 0.8 to 23.2 cc. The addition to individual nodes of a margin of 5 mm was found to result in a mean ENV coverage of ≥95% at all sites. For individual nodes at locations N4R, N5, and N6, however, the coverage ranged from 87.8% to 92.6%.

The addition of a margin of 5 mm to individual mediastinal nodes seems to be adequate to account for variations in both contouring and mobility.     

Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for stage I non-small cell lung cancer?

AIMS AND BACKGROUND: The high local failure rates observed after radiotherapy in stage I non-small cell lung cancer (NSCLC) may be improved by the use of 3-dimensional conformal radiotherapy (3D CRT). MATERIALS AND METHODS: The case-records of 113 patients who were treated with curative 3D CRT between 1991 and 1999 were analysed. No elective nodal irradiation was performed, and doses of 60Gy or more, in once-daily fractions of between 2 and 3Gy, were prescribed. RESULTS: The median actuarial survival of patients was 20 months, with 1-, 3- and 5-year survival of 71, 25 and 12%, respectively. Local disease progression was the cause of death in 30% of patients, and 22% patients died from distant metastases. Grade 2-3 acute radiation pneumonitis (SWOG) was observed in 6.2% of patients. The median actuarial local progression-free survival (LPFS) was 27 months, with 85 and 43% of patients free from local progression at 1 and 3 years, respectively. Endobronchial tumour extension significantly influenced LPFS, both on univariate (P=0.023) and multivariate analysis (P=0.023). The median actuarial cause-specific survival (CSS) was 19 months, and the respective 1- and 3-year rates were 72 and 30%. Multivariate analysis showed T2 classification (P=0.017) and the presence of endobronchial tumour extension (P=0.029) to be adverse prognostic factors for CSS. On multivariate analysis, T-stage significantly correlated with distant failure (P=0.005). CONCLUSIONS: Local failure rates remain substantial despite the use of 3D CRT for stage I NSCLC. Additional improvements in local control can come about with the use of radiation dose escalation and approaches to address the problem of tumour mobility.     

Phase II study of methotrexate,vinblastine, doxorubicin,and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck

BACKGROUND: The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population. METHODS: Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4-week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival. RESULTS: Thirty-six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33-60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1-year progression free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21-63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1-year progression free survival rate was 23% (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate was 54% (95% CI, 33-89%). CONCLUSIONS: Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck.     

Evaluation of Chromosome Aberrations in Subjects Exposed to Environmental Tobacco Smoke in Tamilnadu,India

Numerous expert panels have concluded that there is sufficient evidence to classify involuntary smoking (or passive smoking) as carcinogenic to humans. The aim of this study is to establish whether passive smoking increases the frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes compared to controls in Tamil Nadu, India. In the present study, CA increased with an increase in environmental tobacco smoke (ETS) and active smoke exposure period in passive smokers quantified on the basis of serum cotinine levels. The passive subjects were compared with healthy normal controls to validate the results. In conclusion, these data are compatible with the current knowledge on the mechanisms of carcinogenesis of tobacco-related cancers, occurring not only in active smokers but with a high biological plausibility also in passive smokers.     

The Developing Countries Vaccine Manufacturers' Network (DCVMN) is a critical constituency to ensure access to vaccines in developing countries

Six years after its establishment, the Developing Countries Vaccine Manufacturers' Network (DCVMN) has become the main representing body for emerging vaccine manufacturers from the developing world. The Network's main strategic priority (increase access to DPT-based combination vaccines containing vaccines against Hepatitis B (HepB) and Haemophilus influenzae type b (Hib)) has now come close to fulfillment due in part to the transfer of conjugation technology from The Netherlands Vaccine Institute (NVI) to various manufacturers of the Network. It is argued that at the international level more push mechanisms for product development involving DCVM are needed, including those promoting access to technology and transfer of technology, know how and technical skills from Organization for Economic Co-operation and Development (OECD) countries to developing countries. At the national level, governments of countries in which DCVMN manufacturers operate should provide more generous funding for all aspects of vaccines and immunization including incentives to manufacturers to develop and import new technologies. These two approaches will contribute to the long-term viability of domestic or regional vaccine manufacturing, which in itself is critical to ensure global equity of access to vaccines.