Technical aspects of radiation therapy for anal cancer

Historically treated with surgery, current practice recommends anal carcinoma to be treated with a combination of chemotherapy and radiation. This review will examine the anatomy, modes of disease spread and recurrence, and evaluate the existing evidence for treatment options for these tumors. An in-depth examination of specific radiation therapy (RT) techniques—such as conventional 3D-conformal RT and intensity-modulated RT—will be discussed along with modern dose constraints. RT field arrangement, patient setup, and recommended gross and clinical target volume (CTV) contours will be considered. Areas in need of further investigation, such as the role in treatment for positron emission tomography (PET) will be explored.     

Pharmacological modulation of wound healing in experimental burns

Factors involved in wound healing and their interdependence are not yet fully understood; nevertheless, new prospects for therapy to favor speedy and optimal healing are emerging. Reports about wound healing modulation by local application of simple and natural agents abound even in the recent literature, however, most are anecdotal and lack solid scientific evidence. We describe the effect of silver sulfadiazine and moist exposed burn ointment (MEBO), a recently described burn ointment of herbal origin, on mast cells and several wound healing cytokines (bFGF, IL-1, TGF-beta, and NGF) in the rabbit experimental burn model. The results demonstrate that various inflammatory cells, growth factors and cytokines present in the wound bed may be modulated by application of local agents with drastic effects on their expression dynamics with characteristic temporal and spatial regulation and changes in the expression pattern. Such data are likely to be important for the development of novel strategies for wound healing since they shed some light on the potential formulations of temporally and combinatory optimized therapeutic regimens.     

Impact of metformin use on survival in locally-advanced,inoperable non-small cell lung cancer treated with definitive chemoradiation

Background

We investigated survival outcomes in diabetic patients with non-small cell lung cancer (NSCLC) treated with concurrent metformin and definitive chemoradiation.

Methods

This single-institution, retrospective cohort study included 166 patients with NSCLC who were treated definitively with chemoradiation between 1999 and 2013. Of 40 patients who had type II diabetes, 20 (50%) were on metformin, and 20 (50%) were not on metformin. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Kaplan Meier method and log-rank test were performed in survival analysis. Cox regression was utilized in univariate analysis of potential confounders.

Results

Median follow-up was 17.0 months. Compared with non-diabetic patients, diabetic patients on metformin demonstrated similar OS (16.3 vs. 14.3 mo, P=0.23), PFS (11.6 vs. 9.7 mo, P=0.26), LRRFS (14.1 vs. 11.9 mo, P=0.78), and DMFS (13.4 vs. 10.0 mo, P=0.69). Compared with diabetic patients not on metformin, diabetic patients on metformin also exhibited similar OS (14.3 vs. 19.2 mo, P=0.18), PFS (19.7 vs. 10.1 mo, P=0.38), LRRFS (11.9 vs. 15.5 mo, P=0.69), and DMFS (10.0 vs. 17.4 mo, P=0.12). Identified negative prognostic factors on included squamous cell histology, lower performance status, higher T stage, and non-caucasian ethnicity.

Conclusions

No statistically significant differences in survival or patterns of failure were found among the three cohorts in this small set of patients. No statistically significant differences in survival or patterns of failure were found between the three cohorts in this small set of patients. Though it is possible that metformin use may in fact have no effect on survival in NSCLC patients treated with definitive RT, larger-scale retrospective and prospective studies are implicated for clarification.     

Non-operative therapies for colorectal liver metastases

Locoregional therapies for colorectal liver metastases complement systemic therapy by providing an opportunity for local control of hepatic spread. The armamentarium for liver-directed therapy includes ablative therapies, embolization, and stereotactic body radiation therapy. At this time, prospective studies comparing these modalities are limited and decision-making relies on a multidisciplinary approach for optimal patient management. Herein, we describe multiple therapeutic non-surgical procedures and an overview of the results of these treatments.     

Polypropylene midurethral tapes do not have similar biologic and biomechanical performance in the rat

OBJECTIVES: To evaluate the biomechanical properties and histologic changes of different commercially available polypropylene midurethral tapes (MUTs) after implantation in the rat. METHODS: Pieces of Advantage, intravaginal slingplasty (IVS), suprapubic arch sling (SPARC), and tension-free vaginal tape (TVT) were implanted over the rectus fascia of rats, with six rats serving as controls. On retrieval 24 wk later, the degree of adherence and sample measurements were recorded. Biomechanical testing of the retrieved samples was performed using the uniaxial loading method. Histologic evaluation of the samples under light microscopy included the following parameters: inflammatory infiltrate, fibrosis, mast cell presence, muscular infiltration, and collagen filling of the mesh. RESULTS: No mesh extrusion or infection was encountered. The biomechanical and histologic results were consistent within each group. TVT displayed peculiar adherence characteristics not found among the other brands. No statistically significant difference were found in mean peak load and extension at peak load among the four tested brands. Stiffness of TVT was significantly lower than that of each of the other three brands. Stiffness of Advantage was significantly higher than that of SPARC. The histologic findings differed from one MUT brand to another. By grading certain histologic parameters, an untested model to assign a score for biocompatibility potential in the rat, to different MUTs, was developed. CONCLUSIONS: Commercially available polypropylene MUTs display different biologic and biomechanical properties in the rat.     

Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn’s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.     

Polymerase chain reaction identification of coagulase-negative Staphylococci and of strain diversity and spread of Staphylococcus epidermidis in a major medical center in Lebanon.

A 2-step polymerase chain reaction (PCR) assay and random amplification of polymorphic DNA (RAPD) analysis, respectively, were assessed to identify coagulase-negative staphylococci organisms to the species level and to determine the strain diversity and spread of Staphylococcus epidermidis, the most frequently isolated species, in a medical center in Beirut, Lebanon. Our data indicated that PCR was faster and was more efficient in identifying S. epidermidis isolates than is conventional biochemical testing. RAPD analysis have shown that S. epidermidis strains were scattered across the different clinical services, demonstrating various clusters of infection in the medical center.     

Bone metabolism in obese rats programmed by early weaning

Objective

Obesity and osteoporosis seem to have a common pathogenesis, especially because bone and adipose tissue have common origins. Since early weaning (EW) decreases adipogenesis and osteogenesis in neonate, further programming for obesity and hyperleptinemia, we hypothesized that these changes in adipogenesis could affect bone metabolism.

Materials/Methods

Lactating rats were separated into 3 groups: control — dams whose pups ate milk throughout lactation; mechanical EW (MEW) — dams were involved with a bandage interrupting suckling in the last 3 days of lactation; pharmacological EW (PEW) — dams were bromocriptine-treated (0.5 mg/twice a day via intraperitoneal injection) 3 days before weaning. The adult offspring was subjected to dual-energy X-ray absorptiometry and bone tissue was also evaluated by computed tomography, microcomputed tomography and biomechanical tests, beyond serum analyses.

Results

MEW and PEW presented higher total bone mineral density (BMD), total bone mineral content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both groups also presented increase of these parameters and higher femur BMD and fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral body radiodensity, trabecular number, stiffness and break load; lower trabecular separation, maximal deformation and break deformation, and also hyperleptinemia and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was lower for both groups.

Conclusions

Since both models program for obesity and increased bone mass, and leptin increases plasma vitamin D levels, probably leptin is the link between obesity and higher bone mass.     

Modulation of wound contracture α‐smooth muscle actin and multispecific vitronectin receptor integrin αvβ3 in the rabbit's experimental model

The myofibroblast, a major component of granulation tissue, is a key cell during wound healing, tissue repair and connective tissue remodelling. Persistence of myofibroblasts within a fibrotic lesion leads to excessive scarring impairing function and aesthetics. Various wound‐healing cytokines can be modulated by topical application of active agents to promote optimal wound healing and improve scar quality. Thus, the myofibroblast may represent an important target for wound‐healing modulation to improve the evolution of conditions such as hypertrophic scars. The purpose of this work is to study the modulation of myofibroblasts and integrin αvβ3 in a full thickness wound performed on rabbits treated with different topical agents using: (1) saline, (2) Tegaderm occlusive dressing (3) silver sulfadiazine and (4) moist exposed burn ointment (MEBO). The reepithelialisation was 4 days faster in the MEBO group compared with the other therapies with less oedema formation, delayed contraction, less inflammatory cells and the lowest transepidermal water loss (TEWL) resulting in a soft scar. Although α‐smooth muscle actin (α‐SMA) was the highest around day 12 in the MEBO group, wound contraction and myofibroblast's activity were the least for the same period probably because of a downregulation of the integrin αvβ3. It seems that the effect of MEBO could be more pronounced on force transmission rather then on force generation. Greater insight into the pathology of scars may translate into non surgical treatments in the future and further work in myofibroblast biology will eventually result in efficient pharmacological tools, improving the evolution of healing and scar formation.