Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients

Purpose

The aim of this systematic review was to analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (RT) (morning versus late afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide.

Methods

A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, no guideline possible.

Results

A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and/or conflicting evidence.

Conclusions

None of the agents reviewed was determined to be effective for the prevention or treatment of OM. Two agents, pilocarpine and pentoxifylline, were determined to be ineffective, in the populations listed above. Additional well-designed research is needed on other interventions.     

Comparison of the effectiveness of MRI perfusion and fluorine-18 FDG PET-CT for differentiating radiation injury from viable brain tumor: a preliminary retrospective analysis with pathologic correlation in all patients

ObjectivesDifferentiating radiation injury from viable tumor is important for optimizing patient care. Our aim was to directly compare the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) and dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance (MR) perfusion in differentiating radiation effects from tumor growth in patients with increased enhancement following radiotherapy for primary or secondary brain tumors.Materials and methodsWe retrospectively identified 12 consecutive patients with primary and secondary brain tumors over a 1-year period that demonstrated indeterminate enhancing lesions after radiotherapy and that had undergone DSC MR perfusion, FDG PET-CT, and subsequent histopathologic diagnosis. The maximum standardized uptake value (SUV) of the lesion (SUV_{lesion max}), SUV_ratio (SUV_{lesion max}/SUV_{normal brain}), maximum relative cerebral blood volume, percentage of signal intensity recovery, and relative peak height were calculated from the positron emission tomography and MR perfusion studies. A prediction of tumor or radiation injury was made based on these variables while being blinded to the results of the surgical pathology.ResultsSUV_ratio had the highest predictive value (area under the curve=0.943) for tumor progression, although this was not statistically better than any MR perfusion metric (area under the curve=0.757–0.829).ConclusionsThis preliminary study suggests that FDG PET-CT and DSC MR perfusion may demonstrate similar effectiveness for distinguishing tumor growth from radiation injury. Assessment of the SUV_ratio may increase the sensitivity and specificity of FDG PET-CT for differentiating tumor and radiation injury. Further analysis is needed to help define which modality has greater predictive capabilities.     

Postoperative imaging after lung transplantation

Lung transplantation (LT) is an established procedure for chronic end-stage lung diseases. Complications are frequent and diverse and are the consequence of the complex surgical technique, the severity of the initial pathology, and the deep state of posttransplantation immunosuppression. Complications following LT include primary graft dysfunction, rejection (hyperacute, acute, and chronic), infections, posttransplantation lymphoproliferative disease, pleural and airway complications, native lung complications, and recurrence of primary disease. An understanding of these complications, their temporal evolution, and the role of radiology and other diagnostic methods in their diagnosis and management will help reduce the morbidity and mortality associated with LT.     

Positron emission tomography in the assessment of left ventricular function in healthy rats: A comparison of four imaging methods

Objective

To measure left ventricular (LV) function parameters in heart of healthy rats by three different positron emission tomography (PET) imaging techniques and by magnetic resonance imaging (MRI).

Methods

ECG-gated microPET examinations were obtained in seven healthy rats with 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) for calculation of LV-function from the blood-pool phase of the dynamic recording (FDG_BP), and also from the later myocardial uptake (FDG_Myo). On subsequent days, we re-measured LV-function using the novel blood-pool tracer ⁶⁸Ga-albumin (Alb_BP) and again by FDG (FDG_Myo2) in one setting. Cine-MRI examination provided the reference standard measurement.

Results

The mean LV ejection fractions (LVEF) were 56 ± 3 (FDG_BP), 55 ± 3 (FDG_Myo), 56 ± 3 (FDG_Myo2), 57 ± 3 (Alb_BP), and 57 ± 2 (MRI). There were good to excellent correlations found between the LVEF-values as compared to MRI reference standard for FDG_BP (r = 0.71), FDG_Myo (r = 0.86) and Alb_BP (r = 0.88). Both of the blood-pool methods significantly overestimated the magnitudes of end-diastolic-volume and end-systolic-volume, whereas FDG_Myo matched closely to the MRI reference standard. There was no significant bias for both blood-pool methods and a minor negative bias for FDG_Myo regarding the LV ejection fraction (LVEF) when compared to cine-MRI results. There was no significant difference between the means of FDG_Myo and FDG_Myo2 (P = .50).

Conclusions

Relative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer ⁶⁸Ga-albumin.     

Novel Husbandry Techniques Support Survival of Naked Mole Rat (Heterocephalus glaber) Pups

The naked mole rat (NMR) is a small eusocial rodent. Because of its remarkable longevity (maximal lifespan, 32 y) and resistance to cancer, the NMR has emerged as a valuable model for aging and cancer research. However, breeding NMR can be difficult. Here, we report the successful introduction and acceptance of pups into a foreign colony with existing pups of different ages. Among the 7 NMR colonies in our satellite facility, one had a consistently poor record of pup viability, with nearly 100% preweaning mortality in multiple litters born over the course of 2 y. The queen of this colony gave birth to 18 pups in January 2013; by 2 d after parturition, it was evident that the pups were not receiving sufficient nourishment. To salvage the litter, the most vigorous pups were cross-fostered to another queen that had recently given birth. On postparturition day 1 (PD1), two pups from the poorly nourished donor litter were bathed with warm water, rolled in recipient colony bedding, and transferred to the recipient colony, which included 8 PD14 pups. The new pups were accepted by the recipient queen, who continued to produce milk in response to suckling by the donor pups well past the weaning of her own litter. This case report provides evidence of successful cross-fostering of NMR pups despite age differences between donor pups and those in the recipient litter; this technique may prove beneficial to researchers struggling with NMR breeding issues.Abbreviations: NMR, naked mole rat; PD, postparturition dayThe naked mole rat (NMR; Heterocephalus glaber) is the longest-lived rodent, with a maximal lifespan of 32 y.² NMR also are characterized by their extreme resistance to cancer.^1,4,8 These unique qualities make the NMR a valuable model for aging and cancer research. Although multiple NMR colonies have been established at research universities, breeding NMR in captivity is challenging, because this rodent is a true eusocial species, with cooperative brood care and division of labor between reproductive and nonreproductive animals.⁶ NMR colonies are based on a hierarchical arrangement, with a single, dominant breeding queen, one or more breeding males, and several workers.^5,6 In addition, with the exception of dispersive morphs,⁷ NMR tend to be philopatric, remaining in their natal groups throughout life.³ Here we describe a case in which NMR pups born to a queen with lactation problems were fostered successfully by another colony with pups of older age.     

Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.     

Plasticity and cytokinetic dynamics of the hair follicle mesenchyme during the hair growth cycle: implications for growth control and hair follicle transformations

Hair fiber production is the macroscopic end-point of a highly complex set of interactions between the hair follicle's epithelial and mesenchymal components. The nature of this relationship is largely set during hair follicle morphogenesis, but is dramatically revisited in the adult during the unique tissue remodeling events required for hair follicle cycling. Whereas significant attention has focused on the fate of the hair follicle epithelium during these events, associated changes in hair follicle fibroblast subpopulations remain unclear. Here, we present a speculative review that represents a critical and innovative synthesis of the current literature and summarizes a recently submitted original study by the authors, on the nature of hair cycle-dependent fibroblast dynamics and on how perturbations thereof may lead to several clinical manifestations of altered human hair growth.