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BACKGROUND International guidelines do not recommend magnetic resonance imaging (MRI) for all breast cancer patients at primary diagnostics. This study aimed to understand which patient or tumor characteristics are associated with the use of MRI. The role of MRI among other preoperative imaging methods in clinically node negative breast cancer was studied. MATERIAL AND METHODS Patient and tumor characteristics were analyzed in association with the use of MRI by multivariable logistic regression analysis in 461 patients. Primary tumor size was compared between MRI, mammography (MGR), ultrasound (US) and histopathology by Spearman correlation. The delays in surgery and diagnosis were analyzed among patients with or without MRI, and axillary reoperations were evaluated. RESULTS Age (p

Background/aim Sentinel lymph node (SLN) biopsy has become the standard procedure to identify metastases in axillary nodes in breast cancer. Even after careful SLN examination additional micrometastases and isolated tumor cells (ITCs) are sometimes found, resulting in a need for delayed axillary lymph node dissection (ALND). This study was undertaken to assess prognostic factors identifying additional axillary lymph node (ALN) metastases at delayed ALND. Patients and methods To define the impact of late ALND regarding their outcome, 162 breast cancer patients with 169 operated breasts treated between 2010 and 2012 were evaluated, with follow-up through 2016. Data were collected on the patients, histology and biologic profile of the cancer, lymph node involvement, recurrence of breast cancer and adverse effects of ALND. Results With thorough examination and immunohistochemical stainings twenty-nine of 168 SLN biopsies (28 patients, 17% of the patients) showed micrometastases or ITC, and a full ALND was performed at a later time. During these ALNDs 13 to 31 lymph nodes were removed. Additional ALN metastases were found in three (10%) patients. Two (7%) of the 28 patients with triple-negative cancer deceased of metastatic breast cancer. Three patients (11%) reported adverse effects of ALND requiring physiotherapy due to pain, stiffness, swelling or arm oedema. Tumor factors such as molecular subtype (p=0.002), tumor size (p=0.004), and proliferation index (Ki-67) (p=0.003) correlated with higher numbers of ALN metastases. Conclusion Since most patients with micrometastases found in the primary operation showed no additional positive lymph nodes, completion ALND may not be required in patients with micrometastases or ITCs in the SLN. In our study, the predictive factors for additional ALN metastases were tumur size, molecular subtype and proliferation index. It is conceivable that the features of the primary tumor, rather than the amount of cancer cells in the SLN, might serve to identify patients in whom ALDN can be avoided.

Background A study of the computed tomography (CT) imaging related effective doses and radiation-related cancer death risk. Patients and methods Estimate effective doses were computed from CT scans of testicular cancer patients treated and followed-up in Turku University Hospital, South Western Finland. Association between effective doses from follow-up CT scans and radiation-induced cancer death was examined using United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2008 formula. Results Mean effective dose per CT abdomen was 9.32 (standard deviation, SD 3.89) mSv and for whole-body CT it was 14.24 (SD 6.84) mSv. During follow-up of 6 years, the patients were estimated to undergo 12 to 14 abdominal/whole-body CTs and the corresponding risk estimates were 0.11 and 1.14, respectively. The risk of estimated radiation-induced cancer deaths (RICD in %) computed for mean effective doses was lower in patients diagnosed at older age, being 0.61 for 10-19 years age and 0.04 for 40-49 years age at the diagnosis. Conclusion Patient radiation exposure in CT imaging is associated with the type of CT device and imaging protocols, which should be periodically updated and reviewed to minimize individual exposure. Using the UNSCEAR modelling 2 % risk for radiation related cancer death was attributed to diagnostic exposure of study patients. Age at the diagnosis was associated with CT imaging related radiation exposure. The highest exposure was estimated to the youngest patients.

This study assessed the symptoms and health-related quality of life (HRQOL) of patients with advanced non-small cell lung cancer (NSCLC) and examined the symptom-associated characteristics.The symptoms of 122 patients with NSCLC scheduled for chemotherapy before starting treatment were surveyed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and Edmonton Symptom Assessment Scale (ESAS).The most prevalent symptoms were coughing (EORTC score 41.7), dyspnea (33.9), fatigue (31.9), insomnia (30.3) and pain (21.8). The mean EORTC score for global QoL was 56.9 (SD=23.5). Physical, cognitive and emotional functioning, insomnia, diarrhea, and dyspnea had a significant influence on the HRQOL (p0.05). ESAS assessment correlated with these results and thus was an easy-to-use tool for symptom assessment (correlation coefficient range=0.546-0.865, p0.0001 for all symptoms).Patients with advanced NSCLC suffer from multiple symptoms influencing HRQOL. ESAS provides a symptom assessment tool that is as reliable as but simpler to use than the EORTC questionnaire.

Computed tomography (CT) imaging contributes to a major part of medical radiation exposure. With regard to patients safety, frequent CT examinations (CTEs) performed on the same patient are of particular concern. Tools for tracking the individual patient radiation exposure history and cumulative dose assessment may become important. Here, the applicability of the NRPB-SR250 software was assessed in a retrospective analysis of radiation doses from CTE made consecutively in male patients. Most of the examinations focused on the abdomen or the whole body. The mean number of CTs per patient was 6.8. Significant cumulative effective doses were observed: 76 (66 %) patients received an effective dose higher than 50 mSv, while the maximum was ∼280 mSv. A more than 3-fold effective dose difference was observed between scanners, depending on the scanning protocols. The NRPB-SR250 software proved to be a robust tool for the assessment of organ doses and the effective radiation dose from CT, while challenges were encountered in finding the precise imaging data in retrospective protocols.

Epidemiological studies indicate beneficial effects of flavonoids on cardiovascular disease (CVD) risk. To study the effect of flavonoid-rich sea buckthorn berry (SBB) on circulating lipid markers associated with CVD risk and plasma flavonol concentration. Also investigated was whether changes in the circulating flavonol concentrations correlate with the SBB induced changes in C-reactive protein (CRP) concentration observed previously. In all 229 healthy participants completed the randomized double-blind study and consumed daily 28 g of SBB or placebo for 3 months. Fasting blood samples for the analysis of lipid markers and flavonols were obtained at the beginning and end of the study. Compared to the placebo, the consumption of SBB increased the plasma concentration of the flavonols quercetin and isorhamnetin significantly [treatment differences 3.0 ng/ml (P = 0.03) and 3.9 ng/ml (P

Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. (Less)

Based on randomized studies bone-marrow supported (BMS) high-dose chemotherapy (HDCT) is not superior to conventional CT as adjuvant treatment for high-risk breast cancer. To compare the cost-effectiveness of these treatments we examined the data of Finnish patients in the SBG9401 trial 1. Patients were randomized to receive either dose-escalated (de FEC) (group A, n =59) or FEC and HDCT+BMS (group B, n =70). They received adjuvant radiotherapy (RT) + tamoxifen. All direct health care costs of first line treatment at the oncology units were considered as well as productivity costs within the first 3 years of follow-up. Effectiveness was measured by the number of survival days during 5 years of follow-up. The mean direct health care costs were significantly higher in group B (25829 euro in group A vs. 36605 euro in group B, p0.001), mainly due to a higher number of hospital days. Half of the costs in group A was due to the use of filgrastim (15335 euro in A and 2969 euro in B, p0.001). The costs of RT were only 5% of total costs. There was no statistically significant difference between the groups in the number of survival days, but sensitivity analysis based on bootstrapping suggested that treatment A would be a less costly and more effective alternative in a great majority of cases.

BACKGROUND The adverse effects of hormonal manipulation in prostate carcinoma need to be established in view of its increasing use as an adjuvant treatment. This prospective study investigated the association of androgen deprivation-induced estradiol decline with cognition in prostate carcinoma. METHODS Cognitive testing of prostate carcinoma patients was carried out at baseline and at 6 and 12 months on androgen deprivation (AD). Cognitive performances were evaluated with standardized measures of information processing, including working memory and attention, visual and verbal skills, and memory performances in 31 tests. Testosterone and estradiol changes during AD were measured with the DELFIA® (PerkinElmer, Inc., Wellesley, MA) system. Associations between changes in cognitive performances and estradiol decline were studied. RESULTS Cognitive performances, which were significantly associated with decline in estradiol, included visual memory of figures (r = −0.52; P = 0.022) and recognition speed of numbers, which were impaired, (r = −0.57; P = 0.030) at 6 months, and improvement in verbal fluency (r = −0.52; P = 0.019) at 12 months. Other cognitive domains appeared unaffected by estradiol decline. The character of change (impairment or improvement) depended on the magnitude of estradiol decline. CONCLUSIONS The cognitive domains of verbal fluency, visual recognition, and visual memory were associated with decline in estradiol during androgen deprivation. The results suggest selective associations among testosterone decline, estradiol, and cognitive performance. Documentation of these associations has implications for informed patient support in hormonally treated prostate carcinoma. Cancer 2005. © 2005 American Cancer Society.

Androgen deprivation (AD) used in the treatment of prostate cancer is known to alter concentrations of sex hormones and their binding globulins. Less is known as to its effect on thyroid hormones. In this prospective study the effects of AD on thyroid function were clarified. Levels of serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid binding globulin concentrations were measured in prostate cancer patients treated with either radical radiotherapy and androgen deprivation for 12 months (AD) or radical radiotherapy alone (RT). Measurements were made at baseline, and at 3, 6 and 12 months. At baseline and at 3 months the results of thyroid function tests did not differ significantly between groups. A significant decline in serum testosterone in the AD group was accompanied by a significant decline in FT4 at 6 and 12 months, while no significant changes in thyroid function were observed in the RT group. The decline in FT4 among AD patients did not evoke a normal TSH response. Prolonged use of AD hampers the interpretation of thyroid test results. This finding has substantial implications for the follow-up of patients in hormonally treated prostate cancer.

Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P=0.035; delayed, P

The aim was to evaluate clinical and subclinical cardiac toxicity of epirubicin-docetaxel (ET) combination. Breast cancer patients were given epirubicin (75 mg/m 2 for 15 min), followed 1 h later by a 1-h infusion of docetaxel (75 mg/m 2 ) q3w as first-line treatment Cardiac function was monitored using a 24-h ambulatory electrocardiogram (ECG), left ventricular ejection fraction (LVEF), physical examination and chest radiography. The median LVEF did not decrease during the course of the treatment: median LVEF was 64% prior to treatment and 68% after cycle 8. The 24-h ECG did not reveal any significant changes in heart rate variability. The number of extrasystoles or cardiac arrhythmia did not increase with the ET treatment No patient experienced congestive heart failure during treatment or the mean follow-up of 34 months. We conclude that first-line ET caused no major cardiac changes during 6 months of treatment (8 cycles) or during follow-up. Twenty-four-hour ECG, combined with echocardiography to measure LVEF, was a feasible method for the close monitoring of the cardiac effects during chemotherapy.

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirublcin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m 2 and docetaxel 75 mg/m 2 every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m 2 (range 199-600) and that of epirubicin 476 mg/m 2 (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 × 10 9 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects In a significant number of patients treated for metastatic breast cancer.

The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

Cancer pain management in a hospice setting was studied in the present article. Drug treatments were studied at five time points: at the time of transfer to hospice, at 2nd day, two weeks, and two months following transfer to hospice care, as well as one day before death.Records of 138 consecutive cancer patients treated in hospice in 2010 were studied regarding the drugs given during their stay. The most common cancer was gastro-intestinal cancer (33%), followed by lung (16%) and breast cancer (11%). Data were collected from patients' records and coded in a validated manner for statistical analysis.The median length of stay in hospice was 14 days (range=2-376 days). Upon transfer, 63% of patients were administered regularly-dosed opioids, 76.8% during the second day at hospice, and 89.9% of the patients received opioids one day prior to death. A significant change was observed in the more frequent subcutaneous administration during hospice stay (p0.0001). Break-through pain was recorded on the second day in hospice by 52 % of patients, and by 76% on the day prior to death.Individual patients' needs determined the dose range, but this was not the case for administration route of strong opioids during hospice care.

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor– and/or progesterone receptor–positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P = .0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P = .0006), as was the rate of clinical benefit (49% v 38%; P = .001). Survival data are currently immature and not reported here. Both treatments were well tolerated. CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

This study investigated the outcome of testicular cancer treatment in Finland.Data on 88 testicular cancer patients treated in Turku University Central Hospital between 1976 and 1992 were studied to analyse outcome and survival.The histological diagnosis was seminoma for 39 patients and non-seminoma for 49 patients. Two seminoma patients relapsed (5%) and one patient died of progressive disease (3%; initially stage II seminoma). Eleven non-seminoma patients relapsed (22%), nine of whom were cured with chemotherapy. Four non-seminoma patients died of progressive disease (8%; initially one stage I non-seminoma and three stage III non-seminomas). The median time to relapse after the completion of treatment was 9 months (range 3-50 months). Non-seminoma patients had significantly more relapses than seminoma patients (p = 0.03). Most relapses (73% of the non-seminoma relapses) were found among the stage I non-seminoma patients who had not received adjuvant chemotherapy, while none of the stage I seminoma patients relapsed (p = 0.007).Close surveillance is important for all non-seminoma patients to guarantee the early detection and treatment of recurrent disease. Treatment and surveillance should be covered by national guidelines and be conducted in centres with special interest in this rare but mostly curable cancer.

The cell cycle is a complex event in which multiple regulator-proteins participate. The G 1/S checkpoint of the cell cycle is controlled by pRb protein, which functions in its hypophosphorylated form as a negative regulator of growth. p27 (Kip1), a member of CIP/KIP family of cyclin inhibitory proteins, participates in inhibition of forming complexes that allow pRb to phosphorylate and lead the cell into mitosis. The expression of these important cell cycle regulator proteins was studied in a total of 96 non-Hodgkin’s lymphoma (NHL) samples, which were classified according to the REAL classification. The expression of p27, pRb and the cell proliferation marker Ki-67 (MIB-1) was evaluated in lymphomas using immunohistochemistry. This study showed that there were coordinate changes in the expression of p27 and pRb in NHL. When compared to low-grade lymphomas, high-grade lymphomas showed significantly reduced expression of p27 and inversely pRb expression was increased (P < 0.001). Increase in expression of Ki-67 was parallel with pRb expression, and was mainly seen in cells that lacked p27 expression (P < 0.0001). This study suggests that changes in the control of the cell cycle closely relate to the pathobiology of NHL. © 2000 Cancer Research Campaign

The records of the Finnish Cancer Registry from 1953 to 1994 were used to assess the risk of subsequent primary cancer among 14493 brain tumour patients. They had been treated with surgery only ( n =9804), radiotherapy ( n =4099), chemotherapy and radiotherapy ( n =493) or chemotherapy alone ( n =97). By the end of 1994, 403 subsequent primary cancers were registered in these patients, whilst the expected number based on national incidence was 332. The standardised incidence ratio (SIR) was 1.2 (95% confidence interval (CI) 1.1–1.3). A significant excess risk of tumours in the central nervous system (CNS) including meningeomas (SIR 2.6, 95% CI 1.7–3.8), non-Hodgkin's lymphoma (SIR 2.6, 95% CI 1.6–4.1) and skin melanoma (SIR 1.9, 95% CI 1.0–3.1) was observed. CNS tumours were observed in excess among patients treated with surgery alone (SIR 2.0, 95% CI 1.2–3.2) and with radiotherapy (SIR 5.1, 95% CI 2.5–9.4). In conclusion, brain tumours are associated with an increased risk of both CNS second tumours and non-CNS second cancers, especially non-Hodgkin's lymphoma and melanoma. A moderately increased risk of second tumours in the CNS was observed among brain tumour patients treated with surgery only and a larger excess among those treated with radiotherapy.

In this study, health- related quality of life (HRQoL) and its determinants were assessed in breast cancer patients undergoing postoperative adjuvant radiotherapy. The aim was to improve our understanding of patient’s situation at the end of adjuvant treatment, as the return to every day life approaches after breast cancer surgery and adjuvant chemo- and radiotherapy. Health- related quality of life was measured by the 15D instrument. Self-administered questionnaires were distributed to patients undergoing postoperative radiotherapy. Out of 389 consecutive breast cancer patients, 273 comprised the final study group. The results were compared to 15D results for an age-standardized sample of the female general population in Finland (n = 3,335). Determinants of HRQoL were assessed by a multivariate model. In patients

The risk of a second cancer among lung cancer patients was investigated using Finnish Cancer Registry data from 1953 to 1989. Among the 36 528 patients with a primary cancer of the lung, 504 new cancers were diagnosed six months or more after the diagnosis of lung cancer, yielding a standardized incidence ratio significantly lower than expected (SIR = 0.81). A significant excess of cancers of the larynx (SIR = 2.10) and urinary bladder (SIR = 1.35) was observed. Among lung cancer patients below 60 years of age, the risks of oesophageal cancer (SIR = 2.47) and kidney cancer (SIR = 2.48) were also significantly elevated. The risk of a second cancer among lung cancer patients increased with the length of follow-up, and there was some indication of an excess risk of oesophageal cancer and leukaemia among lung cancer patients subject to radiotherapy.

Lung cancer and mesothelioma are malignant tumors with generally dismal prognosis and therefore palliative pain treatment constitutes a challenge for the clinician.The aim of this study was to compare the outcomes of pain treatment with opioids among mesothelioma and lung cancer patients treated for palliation and assess factors which confound to optimal treatment.A sub-cohort of 373 lung cancer and 22 mesothelioma patients was identified in multi-center European Pharmacogenetic Opioid Study (EPOS) cohort. A nested case-control (1:4) setting was designed to estimate the pain and other covariates distinguishing 22 mesothelioma- (= cases) and 88 lung cancer patients (controls), analyzed using univariate- and multivariate conditional (fixed-effects) logistic regression models.The mean total daily dose of opioids varied from 30.0 to 960.0 mg (mean 275, median 160 mg, SD 293) in mesothelioma, and from 10 to 5072 mg (mean 414, median 175, SD 788) in lung cancer patients (p = 0.420). In both groups, pain was mostly experienced as moderate and severe and it was frequently accompanied by depression, poor sleep, anxiety and fatigue. Four mesothelioma patients (18%) and seven lung cancer patients (10%) experienced complete pain relief with opioids by self-assessment. Assessments of pain severity by the patients and their physicians deviated significantly in mesothelioma (p = 0.039 McNemar test), as well as in lung cancer (p = 0.0001). In conditional logistic regression, no significant differences were found in distribution of pain covariates between lung cancer and mesothelioma patients.Pain perception by the patients was associated frequently with other symptoms and complete pain control with opioids was achieved only with minority of patients both with mesothelioma and advanced lung cancer. Adequate pain control requires continuous monitoring and tailoring the dose to patient's individual needs and tolerance, recognition of accompanying symptoms such as depression and poor sleep, and their management.

The risk of smoking-related secondary cancers developing in bladder cancer patients was studied. The study population consisted of 10,014 bladder cancer patients reported to the Finnish Cancer Registry between 1953 and 1989. The risk of contracting a new primary cancer was estimated as a standardized incidence ratio, defined as the ratio of the observed and expected numbers of cases. Of 660 secondary cancers (6.6%) observed (standardized incidence ratio 0.96) 44% were considered to be smoking-related. Lung cancer was the most common secondary cancer (30% overall), and it occurred significantly more often than expected (standardized incidence ratio 1.31, 95% confidence interval 1.13 to 1.50). Also, larynx cancer among men (standardized incidence ratio 1.67, 95% confidence interval 0.95 to 2.79) and kidney cancer among women (standardized incidence ratio 3.55, 95% confidence interval 1.84 to 6.20) were found more often than expected. These excess risks were observed up to 20 years after diagnosis of bladder cancer. Therefore, bladder cancer patients experience an excess risk of smoking-related new tumors, which must be acknowledged during the initial evaluation and regular followup of such patients.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.