Plesiotherapy for non-melanoma skin cancer: innovating to overcome!

Background:

The non-surgical management of non-melanoma skin cancers is an area requiring clinical investigation. Radiotherapy has a role in treatment for a defined subset of patients.

Aims:

The application of radiotherapy is subject to availability of proper equipment, non-availability of which precludes appropriate radiotherapy in most centers in third world countries.

Materials and Methods:

The introduction of innovations is needed to circumvent this. Plesiotherapy is such a mode of therapy for non-melanoma skin cancer.

Methods:

The introduction of innovations is needed to circumvent this. Plesiotherapy is such a mode of therapy for non-melanoma skin cancer.

Results:

In this paper we present successful management of a cohort of non-melanoma skin cancer patients with plesiotherapy using stepping source¹⁹² Ir HDR source.

Conclusions:

Plesiothrapy is an effective mode of therapy for non-melanoma skin cancer.     

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Background

The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter.

Design and Methods

Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given.

Results

Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse.

Conclusions

This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.     

Integrin-epigenetics: a system with imperative impact on cancer

Integrin-associated signaling is a crucial signaling network in mammalian cells. Thousands of molecules are involved in this signaling network. For example, the RTK, Src-family kinase, Ras, Wnt-, Notch-, and Raft/caveolae-mediated signaling pathways are related to integrin signaling. Integrin signaling is also associated with direct involvement of lipid rafts. Tumor formation, angiogenesis, metastasis, and attachment to distant tissues are largely associated with integrin signaling. Recent evidence has indicated that integrin expression and its functions are tightly regulated by epigenetic mechanisms (modifications of DNA and histones). Aberrations in these epigenetic regulation patterns are frequently associated with the development of various diseases, including cancer. In this review, we discuss influences of integrin signaling along with their epigenetic relationship on other signals of a normal functioning cell and its dysregulation in cancer.     

Adrenal Haemangioblastoma Presenting as Phaeochromocytoma: A Rare Manifestation of Extraneural Hemangioblastoma

Purpose

Adrenal haemangioblastoma presenting clinically as pheochromocytoma is a rare manifestation of extraneural haemangioblastoma. We present an unusual case of von Hippel?CLindau (VHL) disease that had adrenal and cerebellar haemangioblastoma with multiple renal cysts, and a review of the literature.

Methods

Unlike the usual manifestations of secondary polycythemia or increased intracranial pressure and hydrocephalus due to cerebellar lesion, this 36-year-old male presented with hypertension. Investigations revealed right suprarenal mass with raised urinary catecholamines and serum vanillylmandelic acid (VMA) levels, apparently confirming the clinical diagnosis of phaeochromocytoma.

Results

Histopathology of the biopsy specimen showed features of haemangioblastoma, which was confirmed by immunohistochemistry using antibodies to neuron specific enolase and aquaporin-1. Based on this, the patient was screened for possible features of VHL, which revealed cerebellar haemangioblastoma and multiple renal cysts with angiomatous lesion. Postoperative follow-up showed normal levels of catecholamines without any symptoms of phaeochromocytoma.

Conclusions

Adrenal haemangioblastoma is a rare entity with only four cases reported in the literature. Surgical removal is the treatment of choice. However, screening for other possible features of VHL, even in the absence of clinical features, is essential to exclude other potential lesions.     

The neural underpinings of simultanagnosia: disconnecting the visuospatial attention network

Because of our limited processing capacity, different elements of the visual scene compete for the allocation of processing resources. One of the most striking deficits in visual selection is simultanagnosia, a rare neuropsychological condition characterized by impaired spatial awareness of more than one object at time. To decompose the neuroanatomical substrates of the syndrome and to gain insights into the structural and functional organization of visuospatial attention, we performed a systematic evaluation of lesion patterns in a group of simultanagnosic patients compared with patients with either (i) unilateral visuospatial deficits (neglect and/or extinction) or (ii) bilateral posterior lesions without visuospatial deficits, using overlap/subtraction analyses, estimation of lesion volume, and a lesion laterality index. We next used voxel-based morphometry to assess the link between different visuospatial deficits and gray matter and white matter (WM) damage. Lesion overlap/subtraction analyses, lesion laterality index, and voxel-based morphometry measures converged to indicate that bilateral parieto-occipital WM disconnections are both distinctive and necessary to create symptoms associated with simultanagnosia. We also found that bilateral gray matter damage within the middle frontal area (BA 46), cuneus, calacarine, and parieto-occipital fissure as well as right hemisphere parietal lesions within intraparietal and postcentral gyri were associated with simultanagnosia. Further analysis of the WM based on tractography revealed associations with bilateral damage to major pathways within the visuospatial attention network, including the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and the inferior longitudinal fasciculus. We conclude that damage to the parieto-occipital regions and the intraparietal sulcus, together, with bilateral WM disconnections within the visuosptial attention network, contribute to poor visual processing of multiple objects and the loss of processing speed characteristic of simultanagnosia.     

Time course of tinnitus development following noise exposure in mice

Gap-induced prepulse inhibition of acoustic startle (GPIAS) has been used in rats and mice to study the problem of tinnitus. The current study demonstrates that similar methods can be used to study the temporal development of tinnitus over time in middle-aged mice. Six-month-old mice on a mixed C57Bl6 × 129 background were anesthetized with isoflurane and exposed to unilateral noise (n = 15), or sham exposure for controls (n = 8), for 1 hr (16-kHz octave band signal, 116-dB SPL). Tinnitus was tested in eight different sound frequency bands before and at postexposure time points of 1, 3-4, 7, 14, 21, and 30 days and monthly thereafter until 7 months postexposure. Noise-exposed mice displayed a number of changes in GPIAS consistent with the presence of hyperacusis and tinnitus. Noise exposure was associated with acute tinnitus measured 1 day later at several frequencies at and above the exposure frequency center. Consistent, chronic tinnitus then emerged in the 24-kHz range. Several time points following noise exposure suggested evidence of hyperacusis, often followed temporally by the development of deficits in GPIAS (reflecting tinnitus). Temporal development of these changes following noise exposure are discussed in the context of the interactions among aging, noise exposure, and the associated neurochemical changes that occur at early stages of auditory processing.     

Development of a pediatric Level 1 trauma center at a freestanding children's hospital: staff attitudes and perceptions before and after trauma designation

Background

Despite research correlating survival or better outcomes with pediatric trauma care at pediatric hospitals, almost 90% of injured children are treated at predominantly adult facilities. Although the reasons are likely multifactorial, attitudes of pediatric hospital staff may play a role in the development of a pediatric trauma center.

Methods

A survey of hospital staff was conducted to measure the attitude of staff on the effects of becoming a pediatric trauma center. The instrument was administered before and 6 months after trauma center designation. Major topic areas were staffing, organizational impact, education, safety, and financial issues. Attitudes were measured by Likert scale and compared between phases.

Results

A total of 404 staff participated before and 447 staff participated 6 months after designation. Nonphysician respondents dominated the survey respondent pool. Areas of concern included staffing, education, patient volume and acuity, and order and flow. Positive attitudes were seen in areas including quality of care, skill development, and recruitment. Overall improvement in attitudes was observed in several areas.

Conclusions

Hospital staff consistently agreed on the positive impact on quality of care and overall employee benefit. Concerns were mostly diminished at follow-up. A persistent concern of adequate staffing mismatched actual needs. The findings of this study indicate that the staff perceive many measurable benefits to pediatric trauma center development, which have never previously been described.     

Designing of mouse model: a new approach for studying sulphur mustard-induced skin lesions

This study was planned to design a mouse model for studying sulphur mustard (SM)-induced skin injury. SM was applied dermally at dose of 5 or 10 mg kg⁻¹ in polyethyleneglycol-300 (PEG-300) or dimethylsulphoxide (DMSO) or acetone once. The changes in body weight, organ body weight indices (OBWI) and haematological and oxidative stress parameters were investigated over a period of 3-7 days and supported by histopathological observations. Exposure to SM in PEG-300 or DMSO resulted in a significant depletion in body weight, OBWI, hepatic glutathione (GSH) and elevation in hepatic lipid peroxidation, without affecting the blood GSH and hepatic oxidised glutathione (GSSG) levels. Interestingly, no aforesaid change was observed after dermal application of SM diluted in acetone. These biochemical changes were supported by the histological observations, which revealed pronounced toxic effect and damage to liver, kidney and spleen after dermal application of SM diluted in PEG-300 or DMSO. The skin showed similar microscopic changes after dermal application of SM in all the three diluents, however; the severity of lesions was found to be time and dose dependent. It can be concluded that dermal exposure of SM diluted in acetone can be used to mimic SM-induced skin toxicity without systemic toxicity in a mouse model.