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Adequate pain control is essential in cancer treatment. We surveyed Finnish physicians' perception on their skills and training needs on palliative pain management.A structured questionnaire with multiple choices and open ended questions was used for collecting data in 2006-2008. Of 720 physicians participating, 59 were working in oncology and 661 physicians in internal medicine, geriatrics, and primary health care.The principles of the WHO guidelines of cancer pain management were not well known. Forty-six percent of oncologists and 32% of other physicians (P0.0001) knew the analgesic ladder consisting of three steps. Forty-seven percent of oncologists and 61% of other physicians considered pain treatment of cancer patients being well managed in Finland. Only 24% of oncologists and 5% of other physicians considered the education in palliative care being currently at a satisfactory level. Oncologists reported a need of training in interaction and communication skills, ethical questions, and palliative home care. The other physicians expressed the strongest need for training in pain management and palliative care.To have more confidence in treating cancer, pain physicians would benefit in training and education in palliative care. It should be systematically included both in general and specialist training and continuous medical education.

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed. ICARO was organized by the IAEA at the request of the Member States and co-sponsored and supported by other international organizations to assess advances in technologies in radiation oncology in the face of economic challenges that most countries confront. Participants submitted research contributions, which were reviewed by a scientific committee and presented via 46 lectures and 103 posters. There were 327 participants from 70 Member States as well as participants from industry and government. The ICARO meeting provided an independent forum for the interaction of participants from developed and developing countries on current and developing issues related to radiation oncology.

Aims To investigate the pharmacokinetics of finrozole (MPV-2213ad), a novel competitive aromatase enzyme inhibitor, in healthy male volunteers. Methods The study was an open, partly randomized cross-over study including 23 volunteers receiving single doses of 3, 9 mg or 30 mg of finrozole as tablets or solution with 14 days between the administrations. The highest dose was given as tablets only. Serum concentrations of finrozole were determined using high performance liquid chromatography combined with mass spectrometry. Results The mean time to peak serum concentration ranged from 2.5 to 3.1, and 0.6–0.7 h after tablets and solution, respectively. The Cmax values increased as the dose increased. The calculated apparent mean elimination half-life (t1/2,z) was approximately 3 h after the solution, and approximately 8 h after the tablet. The AUC(0,∞) after finrozole tablets increased proportionally from 3 mg to 9 mg and from 3 to 30 mg. The calculated relative mean bioavailabilities (AUC(0,∞)−ratio) for the 3 mg and 9 mg doses of finrozole as tablets were 89% and 78%, respectively. Conclusions The absorption of finrozole from the tablet formulation was relatively rapid, and the apparent elimination half-life was longer after the tablet than after the solution, probably reflecting overlap of the absorption with the elimination phase.

To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC).One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemo- or radiotherapy prior to surgical resection. Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups.The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7 ± 61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P0.01). In contrast, the protein level of p27 was significantly lower in ESCC than in normal squamous epithelium (182.0 ± 69.0 vs 266.4 ± 28.0, P0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0 ± 42.3 vs 83.0 ± 66.5, P0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8 ± 31.7 vs 98.4 ± 84.8, 32.0 ± 19.0 vs 54.1 ± 53.7, 206.2 ± 61.5 vs 123.5 ± 68.3, respectively, all P0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r = 0.270, 0.233 and -0.311, respectively, all P0.05).The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.

Background and purpose The diagnosis and treatment of breast cancer can cause considerable psychological consequences, which may remain unrecognized and untreated. In this study, the prevalence of depressive symptoms and distress, and unmet needs for psychosocial support were assessed among breast cancer patients receiving postoperative radiotherapy. Material and methods Out of 389 consecutive patients, 276 responded and comprised the final study group. Depressive symptoms were assessed with the Beck Depression Inventory. Distress was measured with the Distress Thermometer. Hospital records of the patients were examined for additional information. Results Nearly one third of patients (32.1%) displayed depressive symptoms, and more than a quarter of patients (28.4%) experienced distress. Younger age ( p =0.001) and negative hormone receptor status ( p =0.008) were independent factors associated with distress. One quarter of the patients expressed an unmet need for psychosocial support, which was independently associated with depressive symptoms and/or distress ( p =0.001) and younger age ( p =0.006). Conclusions During radiotherapy for breast cancer, the staff should have awareness of the higher risk of depression and distress in their patients and should consider screening tools to recognise distress and depressive symptoms. Special attention should be paid to younger patients.

Ninety-four urinary bladder cancer patients with locally advanced, recurrent or metastatic urinary bladder cancer were treated with external radiotherapy with the aim of palliating local disease. Conventional radical radiotherapy was inappropriate because of extensive disease, poor general condition or old age of the patients. The palliative course studied was 30 Gy (mid-point dose) in six fractions, two fractions a week. Eighty-two patients (87%) tolerated treatment as planned. Forty patients (43%) had complete palliation of initial symptoms. Thirty-eight patients (40%) had initial local control of the tumour, which was lasting in 25 cases (26%). Median disease-specific survival of the patients was 13. 3 months. The estimated five-year survival was 13% and survival from bladder cancer 27%.

AIM: To investigate the expression of thymidylate synthase (TS) and glutathione-s-transferase π (GST-π) in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS: Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in 28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS: The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples (P < 0.05). The expression level of TS was not only significantly lower in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%, P < 0.05), but was also significantly higher in samples from male patients (46.51%) than from female patients (18.75%, P < 0.05). GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P < 0.05). The expression level of GST-π was also significantly higher in well-differentiated carcinomas (65.63%) than in poorly-differentiated carcinomas (35.00%, P < 0.05). CONCLUSION: The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of TS and reduced expression of GST-π.

One hundred fifty-five patients with urinary bladder cancer who were not suitable for radical surgery were treated with full-course radiotherapy, 6600 cGy in 9 weeks, split-course. After the treatment recurrences were observed in 94 patients (60%), 49 (53%) were treated with transurethral surgery and intravesical cytostatics, local surgery, systemic cytostatics, or palliative radiotherapy. The median survivals for the patients were 33, 10, 4, and 2.4 months, respectively. The outcome of treatment for radiotherapy failures was related to the nature of the failure, ureteric obstruction, the recurrence rate, and the mode of treatment. Shrinkage of the bladder was observed in 15 patients (16%). The occurrence of bladder shrinkage was related to the increase in frequency of recurrences and of different types of treatments.

In a retrospective study, 203 patients with cancer of the urinary bladder were analysed concerning treatment outcome, survival and some prognostic factors. Radiotherapy with curative intent and a tumour dose of 66 Gy in 9 weeks with a 3 weeks' pause after 33 Gy was the planned treatment for 155 patients. Preoperative radiotherapy with a tumour dose of 40 Gy in 4 weeks was delivered to 28 patients, 4-6 weeks prior to cystectomy. Twenty patients with advanced disease received palliative radiotherapy with a tumour dose of 30 Gy in 2 weeks. A significant initial response to radiotherapy was obtained in 26.7% of the patients. The actuarial 5-year survival was 24% for patients treated with definitive radiotherapy only. The most important factors associated with survival in this radiotherapy group were stage (T-class), performance status and serum creatinine. Acute side-effects were common and in 18% of the patients deviation from the planned treatment was necessary.

AIM: To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, infl ammatory bowel disease or diverticulitis. METHODS: A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR. RESULTS: Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. longum and B. bifidum were the most widely found, followed by B. animalis , B. catenulatum and B. adolescentis . B. breve , B. dentium and B. angulatum were not detected in any sample. A signifi cantly higher occurrence of B. longum was observed in patients with diverticulitis than in those with colon cancer or IBD (100%, 62% and 75%, respectively, P < 0.05). Similar results were obtained for B. animalis (56%, 0% and 25%, P < 0.05), while B. adolescentis was only found in the mucosa from patients with colon cancer (5 out of 21, 24%). At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifi dobacterium (4.94 and 5.91 vs 6.96 log Cells/sample, respectively, P < 0.05) and of the species B. longum (4.05 and 4.79 vs 6.76, P < 0.05) than those with diverticulitis. CONCLUSION: Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.

To study the effect of sea buckthorn berries on the number and duration of common cold (CC) infections. As secondary objectives the effects on digestive and urinary tract infections (DTI, UTI), and serum C-reactive protein (CRP) concentrations were also investigated. A total of 254 healthy volunteers were randomly assigned to receive sea buckthorn or placebo product during the study, which 233 of them completed. There were no significant differences in the number or duration of CC or DTI between groups (CC: relative risks (sea buckthorn vs placebo) for the number and duration were 1.15 (95% CI 0.90–1.48) and 1.05 (95% CI 0.87–1.27), respectively). In the sea buckthorn group, as compared to the placebo, the serum CRP concentrations decreased significantly (difference in median change −0.059 mg/l, P=0.039). The number of UTI was too small to draw solid conclusions, but the results indicate the subject merits further investigation. Sea buckthorn berries did not prevent CC or DTI. However, a reductive effect on CRP, a marker of inflammation, and a risk factor for cardiovascular diseases, was detected.

To determine the effects of oat products with increasing beta-glucan content on the glycemic (GI) and insulin indexes (II) of oat products, and to establish the effect of physical properties of beta-glucan on these physiological responses.Test group (n=10) randomly attended to three glucose tolerance tests and glycemic response tests for four oat bran products.Functional Foods Forum and the Department of Food Chemistry, University of Turku, and the Department of Food Technology, University of Helsinki.One male and nine female volunteers were recruited from university students and staff, and all completed the study.GI and II of different products were calculated for each subject using the average of parallel glucose tolerance tests and the subsequent glycemic/insulinemic responses for each product. Average indexes for products were calculated according to the individual data.The glycemic responses to oat products with increasing amounts of beta-glucan had lower peak values than the reference glucose load. The amount of extractable beta-glucan had a high correlation between the glycemic and insulinemic response.In addition to the total amount of beta-glucan in oat products, the amount of extractable beta-glucan in oat products explains the magnitude of the decrease in glycemic responses to carbohydrate products.

The aim of this study was to clarify the association of p53 and Ki-67 protein expressions with tumor characteristics and survival in renal cell carcinoma (RCC).One hundred and seventeen patients were included in the study, 101 (86%) with conventional RCC according to the Heidelberg classification. Patients were divided into three groups with either primary metastases (pm), later metastases (lm), or no metastases (nm) during 7.5 years follow-up. Paraffin-embedded tissues were examined by immunohistochemistry utilizing anti-p53 and anti-Ki-67 antibodies, with a positive reaction cut-off of 10%.In conventional RCC, there was more Ki-67 positivity in high T(tumor)-stage compared to low T-stage (p = 0.036) and in pm patients compared to nm patients (p = 0.007); p53 was not associated with T-stage or metastatic category. Coexpression of p53/Ki-67 was more common in pm patients than in lm patients, but was not observed in nm patients (p = 0.001). In the pm/lm group, p53 and Ki-67 expressions were associated with decreased survival (log-rank, p = 0.030 and p = 0.031, respectively). In lm patients, high T-stage (T3, T4) was associated with metastases-free survival (p = 0.034) and overall survival (p = 0.006).p53 and Ki-67 expressions are associated with aggressive tumor phenotype and decreased survival in metastatic RCC. Ki-67 alone was a stronger prognostic marker than p53 for development of metastases. Double positivity for p53 and Ki-67 expression in RCC patients seems to indicate a high metastatic probability.

Purpose: Non-Hodgkin lymphoma (NHL) occurs in patients in all age groups and its incidence in Finland has constantly increased since the 1950s. In this study the change in the incidence rate and the effect of age on the survival of NHL patients was investigated. The aim of the study was to determine the relative survival by age during follow-up through a cancer registry. Patients and Methods: The data base of the Finnish Cancer Registry was used to collect information of all NHL cases registered in Finland in 1960–1992. A total of 2,824 newly diagnosed cases of NHL were included. Of them 1,414 (50%) were diagnosed in men and 1,410 (50%) in women. Results: The age-specific incidence rates in both sexes indicated a significant increase (p < 0.0001) in incidence for patients from 1960 to 1992. The 1- and 5-year relative survival rates were best for patients diagnosed at the age of 40–44 years. During 10 years’ survival two peaks were observed, in the age group of 20–24 and 40–44 years. The relative survival rate was found to deteriorate with an increase in the age of the patients. Patients with local NHL lymphoma had a similar survival regardless of their age at diagnosis. Relative survival of patients aged over 65 years with extensive lymphoma was 36% of the survival observed for younger patients. Conclusion: There is a trend for an increase in the incidence of NHL. Because NHL is more common in patients over 60 years of age than in the younger age groups, an increasing incidence indicates that more elderly patients will need treatment in the years to come.

The International Atomic Energy Agency (IAEA) is an intergovernmental organization composed by 138 Member States within the United Nations. It has a mandate to seek to accelerate and enlarge the contribution of atomic energy to peace, health and prosperity throughout the world. Within the IAEA structure, the Division of Human Health contributes to the enhancement of the capabilities in Member States to address needs related to prevention, diagnosis and treatment of health problems through the development and application of nuclear and radiation techniques within a framework of quality assurance. In view of the increasing cancer incidence rates in developing countries the activities in improving management of cancer have become increasingly important. This review will outline the IAEA's role in cancer management focusing on activities related to improving radiotherapy worldwide.

Purpose: To assess the risk of esophageal cancer as second cancer among breast-cancer patients treated with radiotherapy. Methods and Materials: The records of the Finnish Cancer Registry from 1953 to 2000 were used to assess the risk of esophageal cancer as second cancer among 75,849 breast-cancer patients. Patients were treated with surgery ( n = 33,672), radiotherapy ( n = 35,057), chemotherapy and radiotherapy ( n = 4673), or chemotherapy ( n = 2,447). The risk of a new primary cancer was expressed as standardized incidence ratio (SIR), defined as the ratio of observed to expected cases. Results: By the end of 2000, the number of observed cases esophageal cancers was 80 vs. 72 expected cases (standardized incidence ratio (SIR) = 1.1, 95% Confidence Interval (CI) = 0.9 to 1.5). Among patients followed for 15 years and treated with radiotherapy, the SIR for esophageal cancer was 2.3 (95% CI=1.4 to 5.4). No increase in risk was seen for patients treated without radiotherapy. The risk of esophageal cancer was increased among patients diagnosed during 1953 to 1974, although age at the treatment did not have marked effect on the risk estimate. Conclusion: Increased risk of second cancer in the esophagus was observed for breast-cancer patients in Finland, especially among patients with over 15 years of follow-up and treated in the earliest period, which may relate to the type of radiotherapy.

Adhesion to the intestinal mucosa is one of the main selection criteria for probiotics. The influence of the endogenous intestinal microbiota on this adhesion has been little investigated. Therefore, the adhesion of five selected probiotic strains to human intestinal mucus with an endogenous microbiota and with a reduced microbiota was assessed. Of the five tested strains, two were found to exhibit an increased adhesion to intestinal mucus with a reduced microbiota. These results suggest that the endogenous mucosal microbiota may only slightly affect the initial adhesion of selected probiotics to intestinal mucus. Key words: probiotic, intestinal mucus, mucosal microbiota, adhesion.

The aim of this study was to assess current management of prostate cancer patients with elevated prostate-specific antigen (PSA) among Finnish urologists and oncologists. Four case scenarios were presented: postprostatectomy PSA relapse, postradiotherapy (RT) relapse with a slowly or rapidly rising PSA, elderly patients prior to treatment. Management preferences and the use of androgen deprivation (AD) in prostate cancer were surveyed. Eighty-two informative replies, 60 from 90 practicing urologists (67%) and 22 from 70 practicing oncologists (31%) were received. For postprostatectomy relapse, salvage RT or follow-up until significant rise of PSA were the favored recommendations. For post RT with slowly or rapidly rising PSA and treatment of non-radical cases an active approach with even small PSA rises and immediate androgen deprivation were favored. For intervention, the recommended PSA border values ranged from 0.5 to > 100 ng/mL. More research is needed focusing on criteria and timing of AD in the treatment of prostate cancer.

Objective: This study investigated self-reported dietary attitudes and changes, and use of complementary approaches among breast cancer patients in relation to age, education and time since diagnosis. Design and setting: Australian (ABC, N=215) and Finnish (FBC, N=139) breast cancer patients were surveyed at the university cancer centres with voluntary participation. Logistic regression models were used to adjust for differences in demographic patient characteristics between the groups. The influence of demographic variables was further studied separately or combined. Results: In all, 30% of FBC patients and 39% of ABC patients reported having changed their diet (P=0.033). Higher education, younger age and longer time from diagnosis were significantly associated with the probability of changes. The main changes reported included reduced consumption of animal fat, sugar and red meat, and increased consumption of fruits and vegetables. In all, 6% of ABC and 4% of FBC patients had stopped smoking and 24% of ABC and 27% of FBC patients reported to have increased their level of physical exercise. Choices were associated with age (P

Their adhesion to the intestinal mucosa is considered one of the main reasons for the beneficial health effects of specific lactic acid bacteria (LAB). However, the influence of disease on the mucosal adhesion is largely unknown. Adhesion of selected LAB to resected colonic tissue and mucus was determined in patients with three major intestinal diseases (i.e., diverticulitis, rectal carcinoma, and inflammatory bowel disease) and compared to healthy control tissue. All strains were observed to adhere better to immobilized mucus than to whole intestinal tissue. Two strains (Lactobacillus rhamnosus strain GG and L. reuteri) were found to exhibit diseasespecific adhesion to intestinal tissue. All tested strains, with the exception of L. rhamnosus strain GG, displayed disease-specific adhesion to intestinal mucus. These results suggest that strains with optimal binding characteristics for a particular intestinal disease can be selected. Specific lactic acid bacteria (LAB) and bifidobacteria have been scientifically shown to be useful for balancing the intestinal microflora and for the management of microflora dysfunctions (20). For many of the health effects, adhesion to the intestinal mucosa is considered important, i.e., antagonism against pathogens (3), transient colonization (1, 15), modulation of the immune system (32), and enhanced healing of damaged intestinal mucosa (4). Adhesion to the intestinal mucosa is therefore considered one of the main properties of the beneficial health effects of selected LAB (13). Fecal levels of lactobacilli and bifidobacteria have been shown to be reduced in patients with inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) (6, 8, 12) as well as in allergy (16), thus suggesting a role for these bacteria in the prevention of these diseases. For a number of gastrointestinal diseases, specific LAB strains have been used successfully. The duration of rotavirus diarrhea has been shown to be reduced by selected lactobacilli (10, 33). Some, but not all, epidemiological studies suggest that the consumption of milk products fermented with LAB may have some protective effect against changes associated with the occurrence of colon cancer (29). Consumption of individual strains of LAB may promote positive changes in humans during CD (17), juvenile chronic arthritis (18), irritable bowel syndrome (22), UC (34), diverticulitis (7), and chronic pouchitis (9). Disturbances in the composition of the intestinal microflora during these diseases can be counteracted with selected LAB (5, 8, 31). As stated above, adhesion to the intestinal mucosa is considered an important component of the beneficial health effects of selected LAB. However, the influence of the disease on the adhesion of LAB is largely unknown. There are a few reports that indicate that the specificities of different LAB may prove to be different in the gut mucosa of patients suffering from different intestinal diseases (1, 19), and these properties can be related to the adhesive capacity of the strains in question. Therefore, we assessed the ability of probiotic and proposed-probiotic LAB to adhere to human intestinal mucosa or intestinal mucus from patients with IBD (CD and UC), diverticulitis, or rectal carcinoma, and we compared these with LAB adhesion to healthy tissue. With this method, disease- and strain-specific differences in the adhesion properties can be identified and will provide new methods for selecting probiotics for specific intestinal dysfunctions.

To explore physiological roles of BCL-W, a prosurvival member of the BCL-2 protein family, we generated transgenic (TG) mice overexpressing Bcl-w driven by a chicken β-actin promoter. Male Bcl-w TG mice developed normally but were infertile. The adult TG testes displayed disrupted spermatogenesis with various severities ranging from thin seminiferous epithelium containing less germ cells to Sertoli cell-only appearance. No overpopulation of any type of germ cells was observed during testicular development. In contrast, the developing TG testes displayed decreased number of spermatogonia, degeneration, and detachment of spermatocytes and Sertoli cell vacuolization. The proliferative activity of germ cells was significantly reduced during testicular development and spermatogenesis, as determined by in vivo and in vitro 5′-bromo-2′deoxyuridine incorporation assays. Sertoli cells were structurally and functionally normal. The degenerating germ cells were TUNEL-negative and no typical apoptotic DNA ladder was detected. Our data suggest that regulated spatial and temporal expression of BCL-W is required for normal testicular development and spermatogenesis, and overexpression of BCL-W inhibits germ cell cycle entry and/or cell cycle progression leading to disrupted spermatogenesis.

Purpose: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. Patients and Methods: This multicenter phase III trial randomly assigned 916 patients with hormone receptor–positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician’s discretion. This report updates efficacy at a median follow-up of 32 months. Results: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P < .0001), time to treatment failure (median, 9 v 5.7 months, respectively; P < .0001), overall objective response rate (32% v 21%, respectively; P = .0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy (“time to chemotherapy”) was significantly longer (P = .005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P = .001). Conclusion: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Purpose: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non–small-cell lung cancer (NSCLC). Patients and Methods: Seventy-three patients with NSCLC underwent [18F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. Results: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P < .0001). Conclusion: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.

The key clinical question in treating cancer patients for palliation is balancing issues on efficacy, toxicity and cost. The costs of chemotherapy have risen substantially during recent years, yet many patients are treated even at the end of their life with unresponsive cancer. The objective of this study was to determine the additional treatment costs during six months on chemotherapy to manage toxicity.Thirty-eight women were treated for metastatic breast cancer with an epirubicin-docetaxel regimen every three weeks. The clinical benefit was calculated for responding and stable patients maintaining the same status for at least 6 months (% of evaluable patients). Data on the use of medical resources were extracted from the hospital records. Health resources utilization analyses included the costs in Euros at year 2000 values during the six months' treatment of all additional hospitalization, drugs and blood transfusions.The response rate (CRIPR) was 54% (95% CI 37-71). Seventy per cent of the patients (95% CI 53-84) had objective clinical benefit. The crude cost of the treatment was 12,416 Euros per patient. The total cost of chemotherapy per patient was 14,915 Euros. The costs of hospital stays, antibiotics, granulocyte growth factors and blood transfusions when indicated added 2,499 Euros per patient, thus adding 20% to crude treatment costs.The treatment of advanced breast cancer with 3-weekly epirubicin-docetaxel combination requires additional use of health resources mainly due to infections. The clinical benefit and true cost rates should be reported with the results of novel schedules.

This study investigated ideas and attitudes of breast cancer patients in two countries with reference to information on diet and their need for dietary counselling.Australian breast cancer (ABC) patients (n=215) surveyed for alterations in dietary habits after diagnosis were compared with breast cancer patients in Finland (FBC; n=139). A validated questionnaire was used. Logistic regression models were used to adjust for differences in demographic patient characteristics between the groups.Eight per cent of FBC and 54% of ABC patients saw diet as a factor contributing to their disease (P0.00001). Thirty per cent of FBC and 39% of ABC reported changing their diet after being informed of the diagnosis (P=0.033). Higher education, younger age and longer (1 year) time to diagnosis were significantly associated with the probability of changing diet among the Australian patients. The main reason given was the desire for cure. The most common source of information was the mass media, and a need for more information on dietary factors relating to disease was expressed by 32% of patients in each group.Ideas about the importance of diet varied significantly among ABS and FBC patients. The lack of precise dietary recommendations for the individual situation was commonly mentioned, and patients depended on information obtained from outside their treatment centre.

Lung cancer is currently the leading cause of cancer-related death in both men and women in most Western countries. Tumour stage is the strongest prognostic factor and the most important parameter guiding treatment decision making. Metabolic positron emission tomography imaging with fluorodeoxyglucose (FDG-PET) has consistently proved superior to conventional imaging for staging of non-small-cell lung cancer and provides information of greater prognostic significance than can be obtained using conventional approaches. FDG-PET has been approved in the USA, Germany and the UK as a basic and invaluable tool in the management of lung cancer.

Breast cancer and rheumatoid arthritis are common diseases which change everyday life among women. This study investigated the beliefs and attitudes of female patients regarding diet and their need for dietary counseling in relation to years since diagnosis, age, and education.Breast cancer (BC) patients were compared to patients with rheumatoid arthritis (RA) with a validated questionnaire. Logistic regression models were used to adjust for the differences in demographic patient characteristics between BC and RA. In addition, the influence of demographic variables was studied further in the BC and RA groups, separately or combined. chi(2) testing was used to analyze the associations between demographic and dietary variables.Eight percent of BC patients and 40% of RA patients considered diet a factor contributing to their disease (P0.0001). Thirty percent of BC patients and 51% of those with RA reported having changed their diet after their diagnosis (P = 0.0003, chi(2)). The patients with RA had a 3.9 times higher assumption on the diet and disease connection compared to breast cancer patients (OR = 3.92, P = 0.002). Longer (5 years) time to diagnosis increased the probability 2.6 times. The main reason for the change in diet was the desire for cure. The main changes reported included reduced consumption of animal fat, sugar, and red meat and increased consumption of fruit and vegetables. The source of information was most commonly the mass media and a need for more information on dietary factors relating to disease was expressed.We observed the patients to express an interest in alternative dietary habits, with the focus on a healthier diet. The lack of precise dietary recommendations for individual disease situations was expressed strongly and patients depended on information from outside their treatment center.

To augment capacity-building for microbiome and probiotic research in Africa, a workshop was held in Nairobi, Kenya, at which researchers discussed human, animal, insect, and agricultural microbiome and probiotics/prebiotics topics. Five recommendations were made to promote future basic and translational research that benefits Africans., published_or_final_version

BACKGROUND Successful treatment of nonsmall cell lung carcinoma (NSCLC) with radical radiotherapy (RT) requires accurate delineation of tumor extent. Conventional computed tomography–based noninvasive staging often estimates intrathoracic thoracic tumor extent incorrectly and fails to detect distant metastasis. High sensitivity and specificity are reported for F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) staging in potentially resectable NSCLC. The authors investigated FDG-PET staging in radical RT candidates with unresectable NSCLC. METHODS The authors prospectively studied 153 consecutive patients with unresectable NSCLC who were candidates for radical RT after conventional staging and had PET scans. Patients were allocated both “before PET” and “after PET” stages. Subsequent management was recorded. Survival analysis was used to compare validity of pre-PET and post-PET staging. RESULTS After PET, 107 patients (70%) actually received radical therapies (radical RT with or without concurrent chemotherapy, n = 102; radical surgery, n = 5); 46 patients (30%) received palliative treatment because of PET-detected distant metastasis (n = 28; 18%) or extensive locoregional disease (n = 18; 12%). Palliative therapies were RT (n = 33), chemotherapy (n = 12), or supportive care (n = 1). All five surgically treated patients underwent potentially curative resections after downstaging by PET. For radically treated patients, post-PET stage (P = 0.0041) but not pre-PET stage (P = 0.19) was strongly associated with survival. Radically treated patients survived longer than those treated palliatively (P = 0.02; 1-year survival, 69% and 44%, respectively; 2-year survival, 44% radical; no palliative patients had 2-yr follow-up). CONCLUSIONS Positron emission tomography–assisted staging detected unsuspected metastasis in 20%, strongly influenced choice of treatment strategy, frequently impacted RT planning, and was a powerful predictor of survival. Potential impact of FDG-PET is even greater in radical RT candidates with NSCLC than in surgical candidates. Cancer 2001;92:886–95. © 2001 American Cancer Society.

An increasing number of women is treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy for breast cancer. The effects of the chemotherapy on many laboratory tests are, however, inadequately known. This study investigates the effects of the treatment on various laboratory tests. Fifteen premenopausal women receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy and optional radiotherapy were included in the study. Common hormonal, biochemical, hematological, protein and lipid laboratory tests were taken serially during a 10-month follow-up. Twelve women became amenorrheic. Their serum follicle stimulating hormone and luteinising hormone concentrations increased accordingly. Other serum hormones (testosterone, androstenedione, sex hormone-binding globulin, prolactin, dehydroepiandrosterone sulfate, cortisol, parathyroid hormone and thyroid hormones) changed only slightly. Hemoglobin concentration and white blood cell count decreased slightly. Serum alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, angiotensin-converting enzyme, amylase, glucose, potassium, phosphate, urea and triglycerides concentrations increased slightly whereas serum bilirubin, haptoglobin, and immunoglobulin A and M decreased slightly. Serum α1-antitrypsin fluctuated around the baseline concentration. Other test results remained at their pretreatment concentrations. With the exception of increases in serum gonadotrophins, the changes observed were slight and the mean concentrations remained within reference limits. Therefore, cyclophosphamide, methotrexate and 5-fluorouracil adjuvant treatment is unlikely to complicate the diagnosis of other diseases.

To study the effects of etoposide on experimental testicular teratoma in 129/SvJ mouse we analysed the tumour growth, differentiation, apoptosis and the localisation of mdr1 P-glycoprotein (mdr1-Pgp). In this model the implanted gonadal ridges developed into testicular teratomas in 17 out of 56 implanted testes (30%) and in 14 out of 28 mice (50%). The tumour-bearing mice were treated with etoposide on 4 successive days either 4 weeks or 6 weeks after implantation, and killed 7 days after the last dose. The mice in the control groups did not receive etoposide. The teratomas consisted mainly of neural tissue. The etoposide-treated 4-week teratomas, but not the 6-week teratomas, were significantly smaller than those in the corresponding control groups. The density of apoptotic cells and the distribution of the mdr1-Pgp were not altered by etoposide. The decreased proportion of immature neuroectodermal tissue components was observed in all treated teratomas, converting the histology towards that of a mature teratoma. In addition, a low proportion of immature tissue components was frequently combined with a low density of apoptotic cells. In conclusion, etoposide decreased the immature tissue components of teratomas, while mature tissues remained unaffected. These results may have clinical relevance in man, since they confirm that postchemotherapy mature teratomas cannot be treated with chemotherapy. Despite benign histology, the human residual tumours have a significant malignant potential and require complete surgical excision and close surveillance.

PURPOSE: The combination of interferon alfa-2a (IFNα2a) plus vinblastine (VLB) induces objective tumor responses in patients with advanced renal cell cancer. However, no prospective randomized trial has shown that this treatment prolongs overall survival. We compared overall survival after treatment with IFNα2a plus VLB versus VLB alone in patients with advanced renal cell cancer. PATIENTS AND METHODS: We prospectively randomized 160 patients with locally advanced or metastatic renal cell cancer to receive either VLB alone or IFNα2a plus VLB for 12 months or until progression of disease. In both groups, VLB was administered intravenously at 0.1 mg/kg every 3 weeks, and in the combination group IFNα2a was administered subcutaneously at 3 million units three times a week for 1 week, and 18 million units three times a week thereafter for the second and subsequent weeks. For patients unable totolerate IFNα2a at 18 million units per injection, the dose was reduced to 9 million units. RESULTS: Median survival was 67.6 weeks for the 79 patients receiving IFNα2a plus VLB and 37.8 weeks for the 81 patients treated with VLB (P = .0049). Overall response rates were 16.5% for patients treated with IFNα2a plus VLB and 2.5% for patients treated with VLB alone (P = .0025). Treatment with the combination was associated with constitutional symptoms and abnormalities in laboratory parameters, but no toxic deaths were reported. CONCLUSION: The combination of IFNα2a plus VLB is superior to VLB alone in the treatment of patients with locally advanced or metastatic renal cell carcinoma. This is the first study to demonstrate that survival can be prolonged by using IFNα2a for these patients.

Novel aromatase inhibitors are developed with requirements of high potency and selectivity for the aromatase enzyme. The hormonal effects of a new, non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were investigated in this study.The study was conducted as a double-blind, placebo controlled phase I study, where 32 healthy male volunteers were randomized to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad or placebo. Serum concentrations of estradiol (E2), testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone were determined from samples taken 0, 4, 8 h and 12 h during the day of drug administration and 1, 2, 4 and 7 days after drug intake. The individual diurnal variation of circulating hormone concentrations was determined in all participants at 0, 4, 8 h and 12 h on the day before drug intake. Specimens for hematological and biochemical analyses were also collected.A dose-dependent and statistically significant (P0.001) decrease in serum E2 concentrations was induced by MPV-2213ad. Lowest mean values were observed 8-12 h after drug administration and at 24 h the reductions were 10%, 34% and 69% from baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18% increase in the placebo group. Serum E2 concentrations returned to baseline within 4 days in all study subjects. A significant increase was observed in the serum concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P0.001) after administration of MPV-2213ad. Serum concentrations of cortisol and aldosterone were unaffected by MPV-2213ad. The drug was well tolerated.Single oral doses of MPV-2213ad, given to healthy male subjects, induced hormonal effects typical for a specific and selective inhibitor of the aromatase enzyme. Importantly, this study design with the determination of the diurnal rhythm in the levels of the corresponding hormones gives additional validity on the results.

Paclitaxel has become part of standard therapy in the treatment of ovarian and breast cancer. Concern has been raised about the effects of paclitaxel on cardiovascular function. Therefore, this study of the effects of paclitaxel on autonomic cardiovascular control was initiated. Eighteen women treated for ovarian or breast cancer were examined with autonomic cardiovascular function tests, once before the treatment and once after the second course of paclitaxel. Heart rate and blood pressure variability and changes in heart rate and blood pressure responses to the tests were measured. Baroreflex sensitivity was calculated from the Valsalva manoeuvre non-invasively. Paclitaxel did not change heart rate variability at rest compared with the pretreatment level. However, medium frequency variability of blood pressure was smaller after treatment with paclitaxel. Paclitaxel treatment did not impair the heart rate and blood pressure responses to the autonomic function tests. The results do imply that paclitaxel alters sympathetic control of blood pressure. Nevertheless, paclitaxel does not appear to precipitate autonomic cardiac neuropathy.

There is a need for an effective and nontoxic chemotherapy for palliative indication in non-Hodgkin's lymphoma (NHL) patients who relapse after conventional or high-dose chemotherapy. The aim of this study was to investigate the feasibility and efficacy of peroral chemotherapy in the palliative treatment of NHL patients.Seventeen NHL patients were treated with peroral trofosfamide (Ixoten) with an initial dose of 50 mg three times daily. The median age of the patients was 62 years (range: 45-78). Most of the patients had received multiple courses of combination chemotherapy.The overall response rate (complete remission and partial remission) was 53% (95% confidence interval 29-77), and median response duration was 7 months. Cross-resistance was not observed between trofosfamide and chlorambucil. Grade 1-3 hematological toxicity occurred in 16 patients. Other side effects, including mild or moderate nausea, neurotoxicity, alopecia and fatigue, did not require dose adjustments. No fatal complications occurred.Trofosfamide as a palliative regimen is feasible and effective in NHL patients even following previous heavy treatment.

The value of daily monitoring of the blood CD34+ cell concentration as a guide to the optimal timing of stem cell harvests was studied in 60 patients who underwent 66 stem cell mobilizations and 189 leukaphereses. There was a highly significant correlation between the blood CD34+ count and the CD34+ cell content in the apheresis product of the same day (r = 0.904, p < 0.01). Thus, the target yield of 4 x 10(6) CD34+ cells/kg can be harvested in one or two leukaphereses when the blood CD34+ cell count exceeds 50 x 10(6)/L. However, an insufficient harvest is to be expected when the blood CD34+ cell count is below 20 x 10(6)/L. The data from 35 autologous blood cell transplantations with a minimum CD34+ cell yield of 1.5 x 10(6)/kg showed that the recovery of blood neutrophil counts to 1.0 x 10(9)/L occurred in all patients within 9-14 days, but the time to recovery of the platelet counts to 20 x 10(9)/L may exceed 14 days, especially if the CD34+ cell content is below 4 x 10(6)/kg. Daily monitoring of blood CD34+ cell counts is a rapid and reliable means to guide the timing of stem cell collections. The count predicts well the CD34+ cell content of the harvests, the number of leukaphereses needed, and the speed of hematopoietic recovery.

The aim of this study was to evaluate the outcome and prognostic factors influencing survival in 106 patients with supratentorial malignant gliomas treated with radiotherapy. The study group included 84 patients treated by surgery and post-operative radiotherapy and 22 patients treated by postbiopsy irradiation. Radiotherapy was delivered to the tumour area with a 2 cm margin, the aimed curative dose was 60 Gy in 6-7 weeks. The 60-month overall survival (Kaplan-Meier) was 20%. Following a univariate analysis, younger age (P < 0.001), longer duration of symptoms (P = 0.009), good performance status after radiotherapy (P < 0.001), other than grade 4 histology (P < 0.001) and higher radiation dose (P < 0.001) were associated with better overall survival rates. Multivariate analysis found that age, symptom duration, histology, extent of symptoms and radiation dose were independent prognostic factors influencing survival. In conclusion, conventional radiotherapy of supratentorial malignant gliomas results in survival that is comparable to results from clinical experiments with different fractionation schedules and radiation with chemotherapy or radiosensitisers. To improve the results, new approaches are needed, especially for patients with the poorest prognosis after standard treatment.

The incidence of a subsequent primary cancer was investigated among 10 014 patients with cancer of the urinary bladder diagnosed in 1953–1989 in Finland. During the follow-up period of 1953–1989, 652 new metachronous cancers were diagnosed. The number equals the expected number based on the national incidence figures. There were 195 second cancers of the lung. The standardised incidence ratio (SIR) for lung cancer was 1.3 among males [95% confidence interval (CI) 1.1–1.4] and 2.6 among females (95% CI 1.4–4.5). An increased SIR for larynx cancer in males (SIR=1.7, 95% CI 0.91–2.8) and for kidney cancer in females (SIR=3.6, 95% CI 1.8–6.2) was observed. The risk of a second cancer was greater among patients less than 60 years of age at the time of first diagnosis than among older patients. No consistent differences were observed in the risk of new cancer between bladder cancer patients treated with or without radiotherapy.

A placebo-controlled double-blind study was conducted on the efficacy of Lactobacillus GG in preventing travellers' diarrhoea. Altogether 820 persons travelling on holiday to southern Turkey to two destinations were randomized into two groups receiving either Lactobacillus GG or placebo in identical sachets. On the return flight each participant completed a questionnaire indicating the incidence of diarrhoea and related symptoms during the trip. Of the original group 756 (92%) subjects completed the study acceptably. The overall incidence of diarrhoea was 43.8% (331 cases). The total incidence of diarrhoea in the placebo group was 46.5% and in the Lactobacillus GG 41.0% indicating an overall protection of 11.8%. Protection rates varied between two different destinations with the maximum protection rate reported as 39.5%. Among older age groups there was significantly less diarrhoea when compared to younger travellers. Lactobacillus GG appeared to be effective in reducing the occurrence of travellers' diarrhoea in one of the two destinations with no side effects.

The aim of this study was to investigate whether 2-(F-18)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) could reliably detect testicular cancer in patients following chemotherapy. Twenty FDG-PET studies were performed on 15 patients with metastatic seminoma or non-seminoma. Tracer uptake in the PET study was measured by calculating the standardised uptake value (SUV) for the tracer. Nine lesions out of 20 were judged to be positive based on high FDG uptake. Three proved to represent inflammatory changes in non-cancerous tissue. Eleven PET studies were negative. In one of these, viable tumour was found at retroperitoneal lymphadenectomy. The median SUV values of metastatic tumours and benign residual tumours were 2.7 (range 1.6-9.5, n= 10) and 1.7 (range 0.7-5.5, n= 15), respectively. The large overlap of SUVs between these groups was due to the relatively high FDG uptake in inflammatory tissue (median 4.2, range 2.0-5.5, n = 4). The results indicate that FDG imaging of metastatic testicular cancer after chemotherapy has limited value because of a potentially high accumulation of FDG in inflammatory tissues. @ 1997 Published by Elsevier Science Ltd.

AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor charact-eristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cyclin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors. METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immun-ohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (×200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections. RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immuno-staining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t = 13.32 and t = 7.52, respectively, P