Evidence based whole breast hypo-fractionated radiation therapy in patients with early breast cancer.

PURPOSE: The aim of the current study was to evaluate the efficacy and tolerability of hypo-fractionated whole breast radiation therapy in patients with early breast cancer. METHODS: Searching electronically PubMed and the Cochrane Central Register we made a comprehensive literature review regarding the randomized controlled phase III trials for hypo-fractionated radiation therapy in early breast cancer. RESULTS: The collected and analyzed data showed that a short course of hypo-fractionated radiation therapy in early breast cancer patients is as effective as the conventional long course regarding tumor response as well as long term side effects. CONCLUSION: More data are needed about the usage and integration of a boost treatment for higher-risk women receiving neo-adjuvant or adjuvant chemotherapy, or the results in special subgroups such as women with large breast size.

Associations of acute-phase reactants with metabolic syndrome in middle-aged overweight or obese people.

BACKGROUND: Metabolic syndrome, i.e. the clustering of visceral obesity, dyslipidemia, hyperglycemia, and hypertension, has become a major public-health challenge worldwide. An acute-phase reactant is one whose level increases by 25% of the standard value during inflammation. Associations of acute-phase reactants with the components of metabolic syndrome among overweight or obese patients has rarely been examined. MATERIAL/METHODS: The CRP, ferritin, fibrinogen, haptoglobin, and ESR levels of 117 consecutive overweight or obese patients were measured. Metabolic syndrome was defined if central obesity was combined with at least two of the following factors: triglyceride level > or = 150 mg/dl or specific treatment for this abnormality, HDL cholesterol < 40 mg/dl in males and < 50 mg/dl in females or specific treatment for this abnormality, systolic/diastolic blood pressures > or = 130/85 mmHg or treatment of previously diagnosed hypertension, and fasting plasma glucose > or = 100 mg/dl or previously diagnosed type 2 diabetes. RESULTS: Eighty-two patients were characterized as having metabolic syndrome and 35 as healthy controls. CRP, haptoglobin, and ESR levels increased with increasing number of components of metabolic syndrome. Ferritin and fibrinogen, in contrast, were increased in patients with metabolic syndrome but did not correlate with the number of components. CONCLUSIONS: CRP, haptoglobin, and ESR may add significant information regarding the severity of metabolic syndrome among overweight and obese patients.

Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article.

Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) which have a combined incidence of 5-8/100,000 population, represent the most common primary central nervous system tumors. The treatment outcomes even with aggressive approach including surgery, radiation therapy and chemotherapy are dismal with median reported survival is less than 1 year. Temozolomide is a new drug which has shown promise in treating malignant gliomas and other difficult-to-treat tumors. This drug is a per os (p.o) imidazotetrazine second-generation alkylating agent which represents the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation. The efficacy of temozolomide was tested in vitro studies and has demonstrated schedule-dependent antitumor activity against highly resistant malignancies, including high-grade glioma (HGG). In addition, in clinical studies, temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative minimal myelosuppression that is rapidly reversible, and activity against a variety of solid tumors in both children and adults. Moreover, preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O(6)-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma. At the present time temozolomide is approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy. Temozolomide's characteristics which make it a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types are its predictable bioavailability and minimal toxicity. An overview of the mechanism of action of temozolomide and a summary of results from more important randomized controlled clinical trials in high grade gliomas are presented here.

Granulosa cell tumor of the ovary: tumor review.

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.

Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review.

Capecitabine (Xeloda) was developed as a pro-drug of fluorouracil (FU), with the aim of improving tolerability and intratumor drug concentrations through its tumorspecific conversion to the active drug. The purpose of this paper is to review the available information on capecitabine, focusing on its clinical effectiveness against various carcinomas. Identification of all eligible English trails was made by searching the PubMed and Cochrane databases from 1980 to 2007. Search terms included capecitabine, Xeloda and cancer treatment. Nowadays, FDA has approved the use of capecitabine as a first line therapy in patients with metastatic colorectal cancer when single-agent fluoropyrimidine is preferred. The drug is also approved for use as a single agent in metastatic breast cancer patients who are resistant to both anthracycline and paclitaxel-based regimens or when further anthracycline treatment is contraindicated. It is also approved in combination with docetaxel after failure of prior anthracycline-based chemotherapy. In patients with prostate, pancreatic, renal cell and ovarian carcinomas, capecitabine as a single-agent or in combination with other drugs has also shown benefits. Improved tolerability and comparable efficacy, compared with the intravenous FU/LV combination, in addition to its oral administration, make capecitabine an attractive option for the treatment of several types of carcinomas.

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.

Colorectal cancer screening awareness among physicians in Greece.

BACKGROUND: Data comparison between SEER and EUROCARE database provided evidence that colorectal cancer survival in USA is higher than in European countries. Since adjustment for stage at diagnosis markedly reduces the survival differences, a screening bias was hypothesized. Considering the important role of primary care in screening activities, the purpose of the study was to investigate the colorectal cancer screening awareness among Hellenic physicians. METHODS: 211 primary care physicians were surveyed by mean of a self-reported prescription-habits questionnaire. Both physicians' colorectal cancer screening behaviors and colorectal cancer screening recommendations during usual check-up visits were analyzed. RESULTS: Only 50% of physicians were found to recommend screening for colorectal cancer during usual check-up visits, and only 25% prescribed cost-effective procedures. The percentage of physicians recommending stool occult blood test and sigmoidoscopy was 24% and 4% respectively. Only 48% and 23% of physicians recognized a cancer screening value for stool occult blood test and sigmoidoscopy. Colorectal screening recommendations were statistically lower among physicians aged 30 or less (p = 0.012). No differences were found when gender, level and type of specialization were analyzed, even though specialists in general practice showed a trend for better prescription (p = 0.054). CONCLUSION: Contemporary recommendations for colorectal cancer screening are not followed by implementation in primary care setting. Education on presymptomatic control and screening practice monitoring are required if primary care is to make a major impact on colorectal cancer mortality.

Old habits die hard: chest radiography for screening purposes in primary care.

OBJECTIVE: To assess whether the use of chest radiography for screening changes over time. DESIGN: Systematic review. DATA SOURCES: MEDLINE, ISI, Cochrane Central Register of Controlled Trials, and handsearching of selected journals. REVIEW METHODS: We evaluated whether the proportion of primary care physicians using chest radiography to screen for (1) malignancy in the general asymptomatic population, (2) malignancy in a high-risk subgroup, (3) any disease in the general population, and (4) any disease in a high-risk subgroup changed over time, using random-effects meta-regression analysis. Adjustments for the availability of national guidelines were also performed. RESULTS: Overall, 10% to 90% of primary care physicians reported using chest x-ray for screening. In unadjusted analyses, the proportion of physicians using chest radiography for cancer screening in the general population tended to increase by 0.9% per year (8 studies, n = 4313). The corresponding annual changes were -2.9% for cancer screening in high-risk subgroups (8 studies, n = 2784) and -0.4% regarding screening for any disease in the population (7 studies, n = 2627). No meta-regressions were run for outcome (4) (only 1 study). In the adjusted analyses, there was a decreasing nonsignificant trend for all outcomes. CONCLUSIONS: Despite formal recommendations, many physicians still use chest x-ray for screening, with their number decreasing slowly over time. This practice may be harmful because the positive predictive value of chest radiography is low, and further evaluation of false-positive findings might be associated with increased cost and risk from additional diagnostic or therapeutic interventions.

Screening chest radiography: results from a Greek cross-sectional survey.

BACKGROUND: Public health authorities worldwide discourage the use of chest radiography as a screening modality, as the diagnostic performance of chest radiography does not justify its application for screening and may even be harmful, since people with false positive results may experience anxiety and concern. Despite the accumulated evidence, various reports suggest that primary care physicians throughout the world still prescribe chest radiography for screening. We therefore set out to index the use of chest radiography for screening purposes among the healthy adult population and to analyze its relationship with possible trigger factors. METHODS: The study was designed as a cross-sectional survey. Five thousand four hundred and ninety-nine healthy adults, coming from 26 Greek provinces were surveyed for screening practice habits in the nationwide anticancer study. Data were obtained for the use of screening chest radiography. Impact of age, gender, tobacco exposure, family history positive for malignancies and professional-risk for lung diseases was further analyzed. RESULTS: we found that 20% (n = 1099) of the surveyed individuals underwent chest radiography for screening purposes for at least one time during the previous three years. Among those, 24% do so with a frequency equal or higher than once yearly, and 48% with a frequency equal or higher than every three years. Screening for chest radiography was more commonly adopted among males (OR 1.130, 95% CI 0.988-1.292), pensioners (OR 1.319, CI 1.093-1.593) and individuals with a positive family history for lung cancer (OR 1.251, CI 0.988-1.583). Multivariate analysis confirmed these results. CONCLUSION: Despite formal recommendations, chest radiography for screening purposes was a common practice among the analyzed sample of Greek adults. This practice is of questionable value since the positive predictive value of chest radiography is low. The implementation of even a relatively inexpensive imaging study on a national scale would greatly burden health economics and the workload of radiology departments.

Hemangiopericytoma of the breast: a case report and a review of the literature.

Introduction. Sarcomas of the breast are rare and hemangiopericytoma (HPC) of the breast is even rarer. Case Report. We report a case of a 43-year-old woman who presented with a 4 cm mass in her right breast. Her family history was positive for breast cancer. A fine needle aspiration indicated a malignant vascular tumor. An excision biopsy and frozen section analysis confirmed the presence of an encapsulated mesenchymal tumor. Its morphology and immunohistochemical marker profile were characteristic for a malignant hemangiopericytoma. Thus, she underwent a tumor excision without an axilla sampling. Approximately one year after the surgery the patient is well without local recurrence or metastasis disease to be observed. We also reviewed the literature and discuss the treatment options, characteristics, and immunophenotype of HPC. Conclusions. The accurate diagnosis of HPC depends on the appropriate histological and immunohistochemical examination. Surgical resection is the treatment of choice and due to scarcity of cases and unpredictable biological behavior of these tumors long term follow-up may be warranted.

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.

Capecitabine for locally advanced and metastatic colorectal cancer: A review.

Capecitabine (Xeloda(®)) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specific conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to 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 on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy consisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability profile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.

Embryonal rhabdomyosarcoma of the uterine cervix.

INTRODUCTION: Embryonal rhabdomyosarcoma (RMS) of the uterine cervix is a rare and extremely malignant entity. Generally, embryonal RMS originating in the uterine cervix is usually diagnosed in adolescence. Before the introduction of effective adjuvant chemotherapy, the prognosis of these lesions was poor. We have treated a young woman suffering from this disease using a combination of surgery, chemotherapy and radiation therapy (RT) with excellent results. The medical community should keep in mind that embryonal RMS of the uterine cervix, despite its malignancy and rarity, can be cured if adequate treatment is given. CASE: A case of a young woman aged 20, presenting with vaginal bleeding, is reported. The histological examination revealed embryonal RMS of uterine cervix. The patient was treated with a combination of surgery, chemotherapy and RT. A review in the literature, which is also presented, shows that the combined treatment of embryonal RMS using surgery and multidrug chemotherapy has significantly improved survival. CONCLUSION: Patients with favourable prognostic parameters, such as localised disease without deep myometrial invasion, single polyp and embryonal histologic subtype, can effectively be treated by surgery. Patients with unfavourable prognostic parameters seem to benefit from a multimodality approach including surgery, adjuvant chemotherapy and RT.

Comprehensive management of upper tract urothelial carcinoma.

Urothelial carcinoma of the upper urinary tract represents only 5% of all urothelial cancers. The 5-year cancer-specific survival in the United States is roughly 75% with grade and stage being the most powerful predictors of survival. Nephroureterectomy with excision of the ipsilateral ureteral orifice and bladder cuff en bloc remains the gold standard treatment of the upper urinary tract urothelial cancers, while endoscopic and laparoscopic approaches are rapidly evolving as reasonable alternatives of care depending on grade and stage of disease. Several controversies remain in their management, including a selection of endoscopic versus laparoscopic approaches, management strategies on the distal ureter, the role of lymphadenectomy, and the value of chemotherapy in upper tract disease. Aims of this paper are to critically review the management of such tumors, including endoscopic management, laparoscopic nephroureterectomy and management of the distal ureter, the role of lymphadenectomy, and the emerging role of chemotherapy in their treatment.

Time-trend of melanoma screening practice by primary care physicians: a meta-regression analysis.

OBJECTIVE: To assess whether the proportion of primary care physicians implementing full body skin examination (FBSE) to screen for melanoma changed over time. METHODS: Meta-regression analyses of available data. DATA SOURCES: MEDLINE, ISI, Cochrane Central Register of Controlled Trials. RESULTS: Fifteen studies surveying 10,336 physicians were included in the analyses. Overall, 15%-82% of them reported to perform FBSE to screen for melanoma. The proportion of physicians using FBSE screening tended to decrease by 1.72% per year (P =0.086). Corresponding annual changes in European, North American, and Australian settings were -0.68% (P =0.494), -2.02% (P =0.044), and +2.59% (P =0.010), respectively. Changes were not influenced by national guide-lines. CONCLUSIONS: Considering the increasing incidence of melanoma and other skin malignancies, as well as their relative potential consequences, the FBSE implementation time-trend we retrieved should be considered a worrisome phenomenon.

Vertebral osteomyelitis and native valve endocarditis due to Staphylococcus simulans: a case report.

BACKGROUND: Staphylococcus simulans is a common animal pathogen that occasionally can colonize human skin. Unlike other coagulase-negative staphylococci, S. simulans tends to cause more severe infections that resemble those caused by S. aureus. We present a case of vertebral osteomyelitis and endocarditis due to S. simulans. To the best of our knowledge, this is the first report of vertebral osteomyelitis associated with native valve endocarditis rather than orthopedic surgery. CASE PRESENTATION: A 46-year-old male butcher was admitted to the hospital with a 4-week history of high fever with profound sweating. He reported weakness in his legs and low back pain that compromised his walking ability. Blood cultures yielded Gram-positive cocci on Gram stain. These cocci were identified to the species level as S. simulans, a coagulase-negative staphylococcus. The patient was treated with antibiotics, which were discontinued after 6 months. CONCLUSION: This case illustrates the importance of identifying coagulase-negative staphylococci to the species level. Accurate identification of S. simulans would further help investigations defining its pathogenic role in human infections.

An inverse relationship between cumulating components of the metabolic syndrome and serum magnesium levels.

Metabolic syndrome has been defined as the presence of abdominal obesity combined with 2 of the following factors: hypertension, dyslipidemia, and impaired glucose tolerance, or diabetes mellitus. Magnesium is an essential cofactor for more than 300 enzymes involved in carbohydrate and lipid metabolism. In this study, we enrolled 117 consecutive overweight and obese patients and we measured serum magnesium levels together with fasting serum glucose, high-density lipoprotein cholesterol, and triacylglycerols. A strong inverse relationship between magnesium levels in serum and the presence of metabolic syndrome was noticed. Moreover, magnesium levels decreased as the number of components of metabolic syndrome increased. Also, there is an inverse relationship between serum magnesium levels and high-sensitivity C-reactive protein. We concluded that decreased levels of serum magnesium are associated with increased risk for metabolic syndrome, perhaps by a low-grade inflammation process.

Colorectal cancer screening coverage in Greece. PACMeR 02.01 study collaboration.

BACKGROUND AND AIMS: Colorectal cancer is a major cause of cancer death in European countries and differences in screening implementation may in part explain USA vs European survival differences. Despite the evidence, no study has evaluated the population colorectal cancer screening (CCS) coverage in any European country. We aimed to index the current CCS practices among a large sample of Greek healthy adults. MATERIALS AND METHODS: The study was designed as a cross-sectional survey. Screening practice habits of 5,259 healthy adults, aged 50-80, were surveyed. Both overall and screening practices of stool occult blood test (SOBT), digital rectal examination (DRE), and colonoscopy or sigmoidoscopy (COL/SIG) were analyzed. RESULTS: Of the population analyzed, 90.1% declared that they were interested in cancer prevention activities. Overall SOBT practice rate within the last 2 years was 4.77%. When only screening procedures were analyzed, this percentage shrank to 1.73%. Overall and screening COL/SIG rates within the last 10 years were 8.76 and 1.74%, respectively. The respective proportions of individuals who underwent DRE were 14.54 and 5.2%. Evidence-based screening practices were influenced by age, family history of colorectal cancer, profession, and educational level; however, SOBT and colonoscopy/sigmoidoscopy did not overcome 4.1 and 4.6% in any subpopulation analyzed. CONCLUSION: The level of CCS coverage among the examined sample of Greek adults was discouraging. Surveys among other European countries are encouraged.

Colorectal cancer screening awareness in European primary care.

BACKGROUND: Adjustment for stage at diagnosis markedly reduces USA versus European colorectal cancer survival differences and a screening bias was therefore suspected. Moreover, little is known about colorectal cancer screening habits in European primary care and the history of guidelines implementation. The purpose of the study was to index the overall colorectal cancer screening attitudes of European physicians involved in primary care activities. METHODS: A systematic literature-search was performed in three major medical libraries: PubMed/MEDLINE, ISI web of science, and COCHRANE. RESULTS: We found only five eligible studies, but valuable data were presented only in four. Colorectal cancer screening was recommended by 65-95% of physicians, but the major part of them implemented it only among high-risk individuals; stool occult blood testing was advised by 42-83% and prescription of screening endoscopic modalities was inconsistent. Most European reports found were not eligible and were mainly focused on diagnostic delay in symptomatic subjects rather than on screening procedures among asymptomatic individuals. CONCLUSION: In comparison with European practice, colorectal cancer screening habits of American physicians are to a greater extent rational, evidence-based and well monitored and have a longer tradition in medical care thus allowing better prevention services for asymptomatic individuals.