Prophylactic percutaneous endoscopic gastrostomy in patients with advanced head and neck tumors treated by combined chemoradiotherapy

Context

Few studies have evaluated outcomes of combined chemoradiotherapy for Stage III-IV head and neck squamous cell carcinoma in terms of the use of nutritional support by means of percutaneous endoscopic gastrostomy (PEG).

Objectives

To compare nutritional status and treatment interruption because of acute toxicity in patients with advanced head and neck tumors who were treated by combined chemoradiotherapy and received or did not receive prophylactic PEG tubes.

Methods

This was a retrospective study that evaluated data obtained from a cancer center in Montpellier, France. A total of 139 consecutive patients treated for Stage III-IV head and neck squamous cell carcinoma from January 1, 1998 to June 30, 2003 were evaluated in terms of nutritional status before and after therapy, treatment interruption because of toxicity, and duration of hospitalization.

Results

Seventy-eight of the 139 patients (58%) did not receive prophylactic PEG feeding, and 61 patients (44%) received PEG feeding. Pretreatment nutritional status was worse in the PEG group. Compared with the initial nutritional status, nutritional status at the end of treatment was unchanged in the PEG group and much worse in the group that did not receive the PEG (P < 0.05). Cumulative incidence of treatment interruption because of toxicity was significantly lower in the PEG group than in the no-PEG group (100 and 236 days of interruption, respectively, P = 0.03) and hospitalization was significantly shorter (P = 0.003).

Conclusion

Prophylactic PEG sustains nutritional status and reduces the cumulative incidence of treatment interruption caused by toxicity and duration of hospitalization. A randomized study is warranted to validate these results.     

Walking capacities in multiple sclerosis measured by global positioning system odometer

We used a global positioning satellite technology odometer to determine the maximum objective walking distance capacity (MOWD) of patients with multiple sclerosis (MS). The MOWD correlated with Expanded Disability Status Scale (EDSS) score (r(2) =0.41; P <0.0001), the MSWS-12 scale (r(2) =0.46; P <0.0001), time to walk 10 m (r(2) =0.51; P <0.02) and walking speed (r(2) =0.75; P <0.001). Limitation of walking capacities was measurable up to 4550 m, strikingly above the 500-m limit of the EDSS. This objective odometer is a promising tool for evaluation and follow-up of patients with MS.     

Intra-cardiac lymphoma with right heart failure: a therapeutic emergency in two patients

We report the cases of two patients admitted to the Emergency Department with a clinical picture of right heart failure. An emergency echocardiograph suggested an intra-cardiac tumor which turned out to be a primary intra-cardiac lymphoma in one case, and a diffuse lymphoma principally localised in the heart in the other. Echocardiographic, CT and MRI investigations clarified the sites, as well as anatomical relations and extensions. Histology confirmed the diagnosis, and allowed classification of the lymphoma in order to decide on treatment. A PET scan performed in one patient illustrated the response to treatment. The respective significance of each of these investigations is discussed, in addition to the management. While transthoracic echocardiography remains the key element in the acute management, MRI and PET scans are being used more and more often for determining the character of these lesions, as well as for assisting with therapeutic decisions and for follow-up.     

CD4 T cell help is required for primary CD8 T cell responses to vesicular antigen delivered to dendritic cells in vivo

Insight into the mechanisms by which dendritic cells (DC) present exogenous antigen to T cells is of major importance in the design of vaccines. We examined the effectiveness of free antigen as well as antigen with lipopolysaccharide, emulsified in complete Freund's adjuvant, and antigen encapsulated in liposomes in activating adoptively transferred antigen-specific CD4 and CD8 T cells. When contained in liposomes, 100- to 1000-fold lower antigen amounts were as efficient in inducing proliferation and effector functions of CD4 and CD8 T cells in draining lymph nodes as other antigen forms. CD11c(+)/CD11b(+)/CD205(mod)/CD8alpha(-) DC that captured liposomes were activated and presented this form of antigen in an MHC class I- and class II-restricted manner. CD4 T cells differentiated into Th1 and Th2 effector cells. Primary expansion and cytotoxic activity of CD8 T cells were CD4 T cell-dependent and required the transporter associated with antigen processing (TAP). Finally, adoptively transferred CD4 and CD8 T cells were not deleted after primary immunization and rapidly responded to a secondary immunization with antigen-containing liposomes. In conclusion, encapsulation of antigen in liposomes is an efficient way of delivering antigen to DC for priming of both CD4 and CD8 T cell responses. Importantly, primary CD8 T cell responses were CD4 T cell-dependent.     

Prevention of posterior capsule opacification by the induction of therapeutic apoptosis of residual lens cells

Posterior capsule opacification (PCO) is a common complication of cataract surgery. Using adenovirus(Ad)-mediated gene transfer, we overexpressed the proapoptotic molecules p53, procaspase 3, Bax, and TRAIL to induce therapeutic programmed cell death of residual lens cells to prevent PCO. Overexpressed TRAIL did not induce apoptosis in cultured rabbit lens cells or in human lens cells. Overexpressed p53 induced apoptosis of lens cells in vitro and ex vivo, but was unable to prevent PCO in vivo. Overexpressed procaspase 3 was associated with engagement of many components of the apoptotic pathway, including cleavage of intracellular caspase targets such as PARP and inter-nucleosome DNA fragmentation. Even when only slightly overexpressed, Bax caused apoptosis of transduced rabbit and human lens cells by engaging the mitochondrial pathway, including catalytic activation of the caspases. A single in vivo injection of Ad vectors expressing either Bax or procaspase 3 into the capsular bag at the end of phacoemulsification prevented PCO in rabbits. These experiments show that Ad-mediated Bax or procaspase 3 overexpression is capable of inducing therapeutic programmed cell death in vitro and in vivo in residual lens cells and preventing PCO in a rabbit model of PCO. Manipulation of proapoptotic molecule expression could be a novel gene therapy approach for prevention of PCO.