Muscle Oxygenation During Running Assessed by Broad Band NIRS.

We used spatially resolved near-infrared spectroscopy (SRS-NIRS) to assess calf and thigh muscle oxygenation during running on a motor-driven treadmill. Two protocols were used: An incremental speed protocol was performed in 5-min stages, while a pacing paradigm modulated the step frequency (2.3 Hz [SLow]; 3.3 Hz [SHigh]) during a constant velocity for 2 min each. A SRS-NIRS broadband system was used to measure total haemoglobin concentration and oxygen saturation (SO2). An accelerometer was placed on the hip joints to measure limb acceleration through the experiment. The data showed that the calf desaturated to a significantly lower level than the thigh. During the pacing protocol, SO2 was significantly different between the high and low step frequencies. Additionally, physiological data as measured by spirometry were different between the SLow vs. SHigh pacing trials. Significant differences in VO2 at the same workload (speed) indicate alterations in mechanical efficiency. These data suggest that SRS broadband NIRS can be used to discern small changes in muscle oxygenation, making this device useful for metabolic exercise studies in addition to spirometry and movement monitoring by accelerometers.

Small cell carcinoma of the bladder: a search of the current literature.

PURPOSE: Small cell carcinoma of the urinary bladder (SCC-BL) is an extremely rare malignancy, accounting for < 1% of all bladder tumors. Its prognosis is very poor because of its highly aggressive behavior and high metastatic potential. This study aimed to update the management and outcome of SCC-BL by searching the relevant international literature. METHODS: Relevant studies were identified by searching MEDLINE and the Cochrane Central Register of Controlled Trials using a combination of terms such as small cell carcinoma, bladder cancer, therapeutic approach, radical cystectomy, radiation therapy and chemotherapy. Additional papers were identified from reviewing references of relevant articles. RESULTS: Previously published series have shown that SCC-BL has a significant male predominance, occurs mainly during the 7th and 8th decade of life and macroscopic hematuria is the most common presenting symptom. According to the most important studies, cystectomy alone seems not to be efficient enough for the management of the disease. On the other hand, radiation therapy when combined with chemotherapy is highly effective with increased survival rates. CONCLUSION: Poor prognosis and rarity render disease management complicated. A definitive treatment is not yet established but combined therapy with systemic platinum-based chemotherapy and adjuvant local radiotherapy seems to be the most effective therapeutic approach for limited-stage SCC-BL. Further research is required in order to clarify whether prophylactic cranial irradiation (PCI) should be performed on a regular basis.

Ameloblastoma, a rare benign odontogenic tumour: an interesting tumour review targeting the role of radiation therapy.

Ameloblastoma is known as a benign, slow-growing, rare, odontogenic neoplasm. The solid/multicystic, the unicystic with a fibrous connective-tissue capsule and the peripheral ameloblastoma represent the three well distinguished clinical types of ameloblastoma. Surgical resection with an attempt to achieve adequate free margins constitutes a well documented and accepted treatment modality. Controversies exist, however, with regard to the extent of operative intervention. Patients with inadequate or positive surgical margins or unresectable lesions can be treated with radiation or combined radiation and chemotherapy. The authors present a review of this sparse disease focusing on the special role and efficacy of radiation therapy in its management.

Targeted therapy with bevacizumab (Avastin) for metastatic colorectal cancer.

During the last decade, the development of new drugs known as targeted therapies was the result of a better understanding of the processes involved in the transformation of normal cells into cancer. The term targeted therapy refers to drugs that selectively target specific molecular pathways involved in tumorigenesis or tumour progression. Angiogenesis is important for tumour growth and metastasis, and is an important target for new biological agents. Bevacizumab is a humanised recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumour growth. On February 26, 2004, the Food and Drug Administration approved bevacizumab as first-line treatment for patients with metastatic colorectal cancer (CRC). The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. The efficacy of bevacizumab in the treatment of metastatic CRC is presented in this review article.

Nicotine has implications in different tumors types. Expert's eye making a literature analysis.

In man, nicotine is commonly consumed via smoking cigarettes, cigars or pipes. The addictive liability and pharmacological effects of smoking are primarily mediated by the major tobacco alkaloid nicotine. There are elevated serum cadmium and lead levels in smokers resulting in glomerular dysfunction. There is a constant and direct attack of various cigarette smoke reagents on the oral epithelial cells, which gradually accumulate and may cause a stepwise malignant transformation. The association between cigarettes and lung cancer has been proven by large cohort studies. Tobacco use has been reported to be the main cause of 90% of male and 79% of female lung cancers. Ninety percent of deaths from lung cancer are estimated to be due to smoking. This review describes the implication of nicotine, smoking, smoke extracts and other tobacco constituents on oral cancers, lung cancer and cancers of the urinary tract.

Therapeutic interventions targeting organ preservation in muscle-invasive bladder cancer: a review

Nowadays in modern oncology there is a tendency towards therapies that target organ preservation. Organ preservation protocols have become standard in the treatment of laryngeal carcinoma, oesophageal cancer, breast carcinoma and soft tissue sarcomas. The three-combined therapy consisting of a transurethral resection of the bladder tumour followed by concomitant chemoradiotherapy has been shown to be an attractive alternative for bladder preservation in selected patients with muscle-invasive bladder cancer. In order to evaluate the organ preservation approaches in muscle-invasive bladder cancer we have conducted a comprehensive literature review. Data reported from the studies have shown that bladder preservation therapy with a trimodality approach is safe and effective. Moreover, such an approach provides patients with the opportunity to maintain an intact and functional bladder with a survival rate similar to that of radical cystectomy (AU)

Lymphoma of the testis as primary location: tumour review

Non-Hodgkin's lymphoma as a primary testicular neoplasm accounts approximately 9% of all testicular malignant tumours and about 1-2% of all non-Hodgkin's lymphoma. This neoplasm is the most common malignant tumour of the testis in the elderly. The most common histotype in primary forms is the diffuse large B-cell lymphoma, whereas more aggressive histologies such as Burkitt's lymphoma are principal founded in cases of secondary involvement of the testis. Regarding clinical presentation, the most common sign is a unilateral painless scrotal swelling, sometimes with sharp scrotal pain or hydrocele. In patients with advanced stage, the systematic B symptoms are present in 25-41% of all cases. In 35% of patients, bilateral testicular involvement is detected. In more advanced stages with para-aortic lymph-node involvement, ascites and abdominal pain is evident. Despite the fact that responses to doxorubicin- containing chemotherapy, especially in early stages, show good results, relapses are often seen, and the prognosis of this tumour is very poor. Testicular lymphoma often disseminates to other extranodal organs, such as contralateral testis, central nervous system (CNS), lung, pleura, Waldeyer's ring and soft tissue. For patients with limited disease, the recommended first-line treatment is orchiectomy followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination chemotherapy, with central nervous system (CNS) prophylaxis and prophylactic irradiation of the contralateral testis. In more advanced or relapsed disease, management should follow the worldwide recommendations for nodal diffuse large B-cell lymphoma (DLBCL). Here we present a review of this tumour (AU)

Evaluating the strength of potential misplaced priorities in opportunistic cancer screening practice in Greece.

PURPOSE: Screening is a significant method for cancer control, nevertheless the implementation of non cost-effective screening tests at national level may constitute a major burden to health economics. The purpose of this study was to determine the cancer screening activities of a large sample of the Hellenic population, in a country with opportunistic screening practice. METHODS: A large survey on cancer screening in Greece was organized and conducted by the Panhellenic Association for Continual Medical Research (PACMeR). Screening performance of evidence-based (EB), non-evidence-based (non EB) and of undefined benefit tests was analysed. RESULTS: 7001 individuals were analysed. Eighty-eight percent of males and 93% of females stated that they were interested in cancer screening practices. Gynecological cancer screening was performed in the range of 23-38%. Colorectal cancer screening was rarely performed in both genders (1- 2%), while non-evidence-based tests were regularly performed (urinalysis 50% and chest radiography 15-18%). Full blood count and PSA measurement were widely accepted (over 45% in both genders and 19.5% in males, respectively). Sociodemographic characteristics did not influence the performance of EB tests in males while females' activities were highly influenced by such parameters. CONCLUSION: Opportunistic cancer screening in a primary health care system where national guidelines are missing may cause ambiguous results. Reconsideration of health policy in such cases is mandatory.

Hypofractionated radiotherapy in non small cell lung cancer: a review of the current literature.

Hypofractionated irradiation has an established role in the palliative treatment of patients with advanced medically inoperable non - small cell lung cancer (NSCLC ) and poor performance status. Also hypofractionated radiotherapy merits careful consideration in the curative treatment of patients with Stage I and II disease using contemporary technology. The biological effect of radiation on tumours is increased as the overall treatment time is shortened. Hypofractionated field radiotherapy offers acceptable palliation with minimal toxicity. The rates of palliation for hemoptysis , chest pain , cough and dyspnea reported from studies with very short regimen ( 8,5 Gy x 2 ), are comparable to those of other trials that used more protracted palliative treatment . The observed toxicity is minimal, and no cases of oesophagitis, pneumonitis, or radiation myelopathy developed. The minimal toxicity is a reflection of both the low biologic total dose and the tight RT design. Therefore the radiation side effects appear to be related to the technique of RT delivered rather than the patient's PS. Hence, widely believed dogmas concerning the tolerance of critical structures to conventionally fractionated doses, such as the dose-volume effect, total dose, and time (latency) dependency, has to be re-evaluated for hypofractionated radiation therapy. As well there is data suggesting that the small stages I - II NSCLC are likely to benefit from hypofractionated regimens too. Hypofractionated stereotactic radiotherapy is a new technically complex approach to the treatment of early-stage nonsmall cell lung cancer. It is capable to deliver much higher doses to the cancer than is possible with standard techniques, and as a result, rates of tumour control are high and similar to what can be achieved by surgical resection. Refinements of technique and dose as well as randomized data are required before stereotactic radiotherapy can be endorsed as a standard of care for patients with inoperable peripherally located T1 non small cell lung cancer. A clear advantage of the very short hypofractionated palliative regimen is that it allows patients with a short expected survival time to spend more of their remaining time away from the hospital.

Capecitabine chemotherapy for metastatic colorectal cancer. Chemical structure, combinations and efficacy.

PURPOSE: capecitabine is an oral fluoropyrimidine which had been developed as a pro-drug of fluorouracil (FU), and had shown improved tolerability and intratumor drug concentrations through its tumor-specific conversion to the active drug. Our purpose was to make a comprehensive literature review regarding capecitabine's efficacy in metastatic colorectal cancer. METHODS: we searched the Pubmed and Cochrane databases regarding all available information on capecitabine, focusing on its clinical effectiveness against metastatic colorectal cancer. Special attention was paid on trials that compared capecitabine with standard folinic acid (leucovorin/ LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover, the efficacy of capecitabine alone or in several combinations with other active drugs such as irinotecan and oxaliplatin on metastatic colorectal cancer were also assessed. RESULTS: comparative trials showed that capecitabine is at least equivalent to standard 5-FU/LV combination regarding progression-free and overall survival, expressing at the same time a better tolerability profile with a much lower incidence of stomatitis. CONCLUSION: nowadays it is known that capecitabine can be combined with other active drugs such as irinotecan and oxaliplatin and the combination of oxaliplatin with capecitabine represents a new standard of care for metastatic colorectal cancer.

Radiation therapy for early breast cancer

In women with early-stage breast cancer treated with surgery alone, microscopic residual disease may not be eliminated and can eventually cause life-threatening metastatic recurrence. Radiation therapy has been widely recommended for local control after breast-conserving surgery (BCS) and after a complete mastectomy in women at high risk of recurrence. However, even with widespread support for these recommendations within the medical community, they are not always heeded. Because local recurrence, when detected early, can often be treated with additional surgery alone, some physicians and patients still elect to avoid radiation therapy. It was felt, based upon individual trial data, that radiation therapy did not affect overall survival, but just decreased local relapse. The meta-analysis, published in the December 17/2005 Lancet, analysed individual data from 42,000 women, collected during 78 different randomised trials conducted since 1985. The availability of extensive 15-year survival data allowed the investigators to quantify the relationship between successful local control and long-term survivorship. Moreover, individual trials all show a benefit in local control and some trends toward survival advantages. The pooled meta-analysis of breast conservative surgery with or without radiation therapy Vinh Hung (2004) demonstrates a significant impact on local relapse and a small but significant impact on survival. It is considered that after BCS and in certain cases after mastectomy, radiation therapy is the standard treatment for improved local control and longterm survival (AU)

Post-surgical irradiation causes cellular immune suppression in patients with breast cancer.

According to several studies, even the locoregional irradiation of patients with carcinoma can cause a severe and rather alarming cellular immune defect. We thus designed a prospective research in order to study the effect of post-operative irradiation on cellular immunity in patients suffering from breast cancer. In 35 patients with breast cancer who required post-operative irradiation, four blood samples were taken at indicated point times. Nineteen out of 35 patients received post-surgical chemotherapy before irradiation. The total lymphocytes as well as CD4 and CD8 subpopulations were measured by using flow cytometry analysis. The mean T-lymphocyte (Tol) count dropped from 1487.77 to 1227.91 (P = 0.0013) and the CD4+ count from 674.17 to 580.91 (P = 0.0189). The mean value of CD8+ dropped from 421.31 to 314.00 (P = 0.0003). Moreover, a statistically significant difference regarding the pattern of temporal change was observed between a group of patients that received irradiation only and a group that received radiation therapy (RT) with chemotherapy (P-values 0.0015, 0.01 and 0.092 for Tol, CD4+ and CD8+ respectively). The group of patients that received RT only presented a more rapid decrease of Tol concerning the decrease observed in the group that underwent chemotherapy and RT.

The efficacy of combined treatment with cetuximab (erbitux) and radiation therapy in patients with head and neck cancer.

Squamous cell carcinoma of the head and neck (SCCHN) region is among the most frequent human tumors due to the alcohol and tobacco abuse. Its management has evolved gradually from surgery as the mainstay of therapy to irradiation as the principal treatment. When radiation therapy is combined with chemotherapy, additional benefit is obtained. The value of chemoradiotherapy (CRT) is, however, counterbalanced by increased and often prohibitive toxicity, particularly among patients with coexisting medical conditions and decreased performance status. A member of the ErbB family of receptor tyrosine kinases known as the epidermal growth factor receptor (EGFR) is abnormally activated in epithelial cancers, including head and neck cancers. Overexpression of EGFR is a feature associated with poor clinical outcome. It is observed that radiation increases the expression of EGFR in cancer cells and the blockade of EGFR signaling sensitizes cells to the effects of radiation. The cytotoxic effects of radiation therapy in squamous cell carcinoma could be enhanced by cetuximab (erbitux), a monoclonal antibody against the ligand-binding domain of EGFR. The major studies that focus on the efficacy of adding cetuximab to radiotherapy in the treatment of patients with head and neck cancer and its impact in quality of life are reviewed in this study.

Overview of positron emission tomography chemistry: clinical and technical considerations and combination with computed tomography.

The concept of emission and transmission tomography was introduced by David Kuhl and Roy Edwards in the late 1950s. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania. Tomographic imaging techniques were further developed by Michel Ter-Pogossian, Michael E. Phelps and others at the Washington University School of Medicine. Positron emission tomography (PET) is a nuclear medicine imaging technique which produces a 3-dimensional image or map of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Images of tracer concentration in 3-dimensional space within the body are then reconstructed by computer analysis. In modern scanners, this reconstruction is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine. If the biologically active molecule chosen for PET is 18F-fluorodeoxyglucose (FDG), an analogue of glucose, the concentrations of tracer imaged give tissue metabolic activity in terms of regional glucose uptake. Although use of this tracer results in the most common type of PET scan, other tracer molecules are used in PET to image the tissue concentration of many other types of molecules of interest. The main role of this article was to analyse the available types of radiopharmaceuticals used in PET-CT along with the principles of its clinical and technical considerations.

Responsibilities in cancer preventive care in Greece. A physicians' survey

BACKGROUND: Colorectal cancer is the second leading cause of cancer death in European countries. Differences in screening implementation may explain USA vs. European survival differences. The proportion of European primary care physicians advising colorectal screening has been reported to be inconsistent. We therefore hypothesised the presence of a belief-related bias among European physicians regarding who is responsible for cancer screening delivery. OBJECTIVES: To index beliefs in cancer screening implementation among a wide sample of Greek physicians. Study design Cross-sectional survey. METHODS: Three hundred and sixty-six physicians involved in primary care activities in 15 provinces answered a questionnaire about responsibility in cancer screening delivery. Results 22.4% and 7.6% of physicians declared that the health system and the patients, respectively, have the main responsibility for cancer screening implementation, while 70 % advocated patient-health system co-responsibility. Beliefs were statistically correlated to age (p=0.039) and specialisation category (p=0.002). Patients' will was mainly indicated by internists, trainee internists and physicians older than 30, while GPs, trainee GPs and house officers were mainly health system-oriented. Worryingly, when physicians were asked about which specialty should inform the population, 81% indicated family doctor (for-fee-service) while the involvement of free-from-fee specialities was inconsistent. CONCLUSION: A considerable disorientation about responsibilities in cancer screening delivery was observed in our study sample. Continual medical education and clear redefinition of primary care physicians' activities are required (AU)

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Tumour marker prescriptions for cancer screening in the Hellenic primary care.

Tumour markers are neither sensitive nor specific enough for cancer screening. Despite established guidelines, tumour marker 'screening myth' may be alive among physicians, but no study has analysed the phenomenon. This study aims to investigate tumour marker recommendation for screening purposes in primary care setting. A total of 209 Hellenic physicians were surveyed for screening activities by a multiple-choice questionnaire. Data were abstracted for the following tumour marker recommendations: carcinoembryonic antigen (CEA); cancer antigens 19.9, 125 and 15.3; alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG). A high rate of physicians advocate that tumour markers in cancer screening (range from 24% for beta-HCG to 46% for CEA). This phenomenon is not related to age, sex, type and level of physicians' specialization. In conclusion, many physicians recommend tumour markers for screening purposes. This may be harmful, since their prescriptions unnecessarily burden health economics, and further evaluation of false-positive findings might be associated with increased costs and risk from additional diagnostic/therapeutic interventions.

Concurrent administration of Docetaxel and Stealth liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection.

The substantial augmentation of the radiation sequelae during chemo-radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo-radiotherapy scheme with Stealth liposomal doxorubicin (Caelyx and Docetaxel (Taxotere in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere was 20 mg m(-2) week and of Caelyx was 15 mg m(-2) every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere/Caelyx was, thereafter, increased to 20/25 (five patients) and 30/25 mg m(-2) (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The 'in-field' radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere/Caelyx chemo-radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the 'in-field' toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer.