Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax.

BACKGROUND & OBJECTIVES: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA) in human cutaneous anthrax cases. METHODS: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. RESULTS: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] = 0.9982; slope = 0.9186; intercept = 0.1108). INTERPRETATION & CONCLUSIONS: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.

BACKGROUND: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. METHODS: Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). FINDINGS: After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%. INTERPRETATION: Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

Stereotactic Ablative Radiotherapy Versus Low Dose Rate Brachytherapy or External Beam Radiotherapy: Propensity Score Matched Analyses of Canadian Data.

AIMS: To compare biochemical failure-free survival (BFFS) and overall survival for prostate cancer treated with stereotactic ablative radiotherapy (SABR), low dose rate (LDR) brachytherapy or external beam radiotherapy (EBRT) using a large Canadian multi-institutional database. MATERIALS AND METHODS: Patients with low risk localised prostate cancer treated with SABR, LDR or EBRT and no androgen deprivation therapy were selected. Propensity score matching was used to create two sets of matched cohorts with LDR and EBRT serving as control groups. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare differences in BFFS and overall survival between treatment groups. RESULTS: The pre-matched cohort contained 602 patients; the median follow-up was >5.0 years. There were no significant differences in BFFS before or after matching for SABR versus LDR but the prostate-specific antigen (PSA) nadir was lower after LDR. For the SABR versus EBRT, SABR had a BFFS trend before matching (P = 0.08), which became significant after matching (P < 0.001). CONCLUSIONS: Using the Genitourinary Radiation Oncologists of Canada Prostate Cancer Risk Stratification database, low risk prostate cancer patients receiving SABR had similar BFFS compared with patients receiving LDR but better BFFS than EBRT patients. Further comparative studies of efficacy, quality of life and economic outcomes using a broader risk of patients are warranted.

Maximal androgen blockade for the treatment of metastatic prostate cancer--a systematic review.

INTRODUCTION: Maximal androgen blockade (MAB) versus castration alone in patients with metastatic prostate cancer has been extensively evaluated in randomized trials. The inconsistent results have led to the publication of multiple meta-analyses. The present review examines the evidence from meta-analytic reports to determine whether MAB using agents such as flutamide, nilutamide, and cyproterone acetate (CPA) is associated with a survival advantage. METHODS: We conducted a systematic review of the literature (MEDLINE, EMBASE, and the Cochrane Library through July 2004; CANCERLIT through October 2002) for meta-analyses that compared MAB with castration alone in previously untreated men with metastatic prostate cancer (D1 or D2, N+/M0 or M1). Two reviewers selected papers for eligibility; disagreement was resolved by all the authors through consensus. RESULTS: The literature search identified six meta-analyses that met the eligibility criteria of the review. Two of those reports were based on individual patient data (IPD), and four were based on data from the published literature. All six meta-analyses pooled data on overall survival. The best evidence came from the largest meta-analysis, conducted by the Prostate Cancer Trialists Collaborative Group and based on IPD (8725 patients) from 27 trials. That analysis detected no difference in overall survival between mab and castration alone at 2 or 5 years. However, a subgroup analysis showed that MAB with nonsteroidal anti-androgens (NSAAS) was associated with a statistically significant improvement in 5-year survival over castration alone (27.6% vs. 24.7%; p = 0.005). The combination of MAB with CPA, a steroidal anti-androgen, was associated with a statistically significant increased risk of death (15.4% vs. 18.1%; p = 0.04). Compared with castration alone, MAB was associated with more side effects (that is, gastrointestinal, endocrine function) and reduced quality of life in domains related to treatment symptoms and emotional functioning. CONCLUSIONS: The small survival benefit conferred by MAB with NSAA is of questionable clinical significance given the added toxicity and concomitant decline in quality of life observed in patients treated with MAB. Therefore, combined treatment with flutamide or nilutamide should not be routinely offered to patients with meta-static prostate cancer beyond the purpose of blocking testosterone flare. Monotherapy, consisting of orchiectomy or the administration of a luteinizing hormone-releasing hormone agonist is recommended as standard treatment.

Breast irradiation postlumpectomy: development and evaluation of a decision instrument.

PURPOSE: To develop an instrument to help clinicians inform patients about the benefits and risks of breast irradiation following lumpectomy and to help an informed patient decide whether she prefers this treatment. METHODS: A Decision Board consisting of written material and visual aids was developed. It provides the patient with detailed information about her choices (breast irradiation or not), outcomes (breast recurrence and survival), probability of those outcomes, and quality of life associated with treatment and outcome. We studied the decision-making process in 82 consecutive node-negative lumpectomy patients who were seen in consultation by a radiation oncologist and oncology nurse. The Decision Board was used in the last 30 patients in the cohort. RESULTS: Patient comprehension following the consultation without the Decision Board was greater than 65% for all questions addressed, except for poor understanding of the lack of survival benefit associated with breast irradiation (12% of patients answered correctly) and that it could not be repeated (15% of patients answered correctly). Comprehension following the consultation with the Decision Board was similar, but understanding regarding the repetition of radiation (83%) was improved. Only 70% of patients in the no-Decision Board group felt they were offered a choice. This was increased to 97% in the Decision-Board group. Overall, 95% of patients chose breast irradiation, and this did not differ between groups. Patients reported several reasons for choosing breast irradiation, all of equal importance. CONCLUSION: The Decision Board facilitated shared decision making in node-negative lumpectomy patients who chose breast irradiation, but it did not affect a patient's choice to select breast irradiation.

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer.

PURPOSE: A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases. METHODS AND MATERIALS: The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo. RESULTS: One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor makers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89. CONCLUSIONS: It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality-of-life and need for analgesic support in this group of patients.

Patient preference for high or low dose rate brachytherapy in carcinoma of the cervix.

High and low dose rate are two competing methods of brachytherapy. Existing data do not support choosing one method over the other for treating carcinoma of the uterine cervix. Arguments include clinical efficacy, monetary cost, radiation safety, and patient preference. There are no published data on patient preference. We developed a questionnaire to elicit patient preference and to measure its strength. Subjects received descriptions of both treatment options and their probable outcomes. We elicited preference for one low or three high dose rate fractions, and for two low or five high dose rate fractions, assuming both methods to be isoeffective. Strength of initial preference was measured by asking subjects how much of a change, in either the changes for cure or the chances for toxicity, would make them change preference. The questionnaire was completed by female staff at our centre (n = 90), by a group of previously treated patients (n = 18), and by a group of newly diagnosed patients (n = 20). When both methods were assumed to be isoeffective, only 34% of the 38 patients preferred three fractions of high dose rate to one fraction of low dose rate. However, when high dose rate was assumed to be 2% more curative, or 6% less toxic, a simple majority of 50% then said they would prefer high dose rate. Both preference and strength of preference for low dose rate were significantly associated with a greater travelling distance for treatments. Age, marital status, family structure, education, employment, and family income were not associated. In summary, a majority of our patients preferred low dose rate brachytherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Primitive neuroectodermal tumors of the uterus: a report of four cases.

Four cases of primitive neuroectodermal tumor (PNET) of the uterine corpus are reported, bringing the total number of reported PNETs in this site to seven. The four women were in their seventh decade of life and presented with abnormal vaginal bleeding and, in two cases, an enlarged uterus. The patients underwent total or subtotal abdominal hysterectomy and bilateral salpingo-oophorectomy and, in one patient, pelvic lymphadenectomy. Three patients received postoperative radiation therapy, chemotherapy, or both. Gross examination revealed fleshy polypoid masses filling the endometrial cavity and, in two cases, deeply invading the myometrium. Histologic, immunohistochemical, and, in two cases, ultrastructural examination revealed typical PNETs that exhibited variable degrees of neural, glial, ependymal, and medulloepithelial differentiation. Two PNETs were admixed with other neoplasms: in one case a grade I endometrial adenocarcinoma and in the other a low-grade endometrial stromal sarcoma. The prognosis of the tumors was related to their stage: two patients with stage I tumor were alive with no evidence of disease at 5 and 6 years, whereas two patients with stage III or IV tumor died of tumor at 6 and 12 months. Although it has been suggested that uterine PNETs may be derived from displaced germ cells or implanted fetal tissues, evidence provided by this study, including the advanced ages of the patients and an admixture with neoplasms of unquestioned müllerian origin, suggests a müllerian origin for these tumors in at least some cases.

Combined gamma-irradiation and subsequent cisplatin treatment in human squamous carcinoma cell lines sensitive and resistant to cisplatin.

PURPOSE: To investigate the effects of combined radiation and subsequent cisplatin treatment on the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP. MATERIALS AND METHODS: SCC-25 and SCC-25/CP cells were treated with various gamma-ray doses (5 cGy-7 Gy) followed 60 min later by cisplatin treatment and subsequently assayed for survival using a conventional colony assay. For SCC-25, the subsequent cisplatin treatment was 0.1, 1, 10 and 20 microM for 1 h. For the more cisplatin-resistant SCC-25/CP cells, the subsequent cisplatin treatment was 10 and 50 microM for 1 h. RESULTS: The cisplatin-resistant SCC-25/CP cells were not cross-resistant to gamma-irradiation. Subsequent treatment with an LD50 concentration of cisplatin (10 and 50 microM for SCC-25 and SCC-25/CP, respectively) resulted in radiosensitization for SCC-25/CP but not for SCC-25 cells. Gamma-irradiation of SCC-25/CP cells followed by treatment with 10 and 50 microM cisplatin for 1 h resulted in radiation survival curves displaying a significant low-dose hypersensitive region followed by increased radioresistance at higher doses. A total of 10 microM cisplatin resulted in radiosensitization confined to the low-dose region (0.05 and 0.25 Gy), whereas the higher cisplatin treatment of 50 microM resulted in the appearance of a hypersensitive region together with a reduction of the increased radioresistance region. In contrast, cisplatin treatment (0.1, 1, 10 and 20 microM for 1 h) of SCC-25 cells had no significant effect on survival following 2.5 or 7.0 Gy and actually resulted in an increased low-dose radiation survival (0.05, 0.25 and 1 Gy) when survival was corrected for cisplatin treatment (p<0.01 for all cisplatin concentrations tested). CONCLUSIONS: The significant radiosensitization for SCC-25/CP given subsequent treatment with 50 microM cisplatin indicates cisplatin can inhibit the increased radioresistance response in SCC-25/CP cells. In contrast, the subsequent cisplatin treatment of SCC-25 cells can enhance their survival following low radiation doses.

Pre-exposure of human squamous carcinoma cells to low-doses of gamma-rays leads to an increased resistance to subsequent low-dose cisplatin treatment.

PURPOSE: To investigate low-dose hypersensitivity to cisplatin and increased resistance at higher doses of cisplatin for the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP, and to examine the effects of pre- and post-treatment of SCC-25 cells with low-doses of gamma-rays on their resistance to cisplatin. MATERIALS AND METHODS: SCC-25 and SCC-25/CP cells were treated with various cisplatin concentrations (0.1 to 20 microM for 1 h) and assayed for survival using a conventional colony assay. For SCC-25, various doses of gamma-rays (5 cGy to 2.5 Gy) were given either 10 or 60 min before the cisplatin challenge dose as well as either 10 or 60 min after the cisplatin challenge dose. RESULTS: Low-dose (0.5, 0.75 and 1 microM for 1 h) hypersensitivity to cisplatin and increased resistance at higher doses was detected for the SCC-25 cell line, but not for its cisplatin-resistant derivative, SCC-25/CP. Pretreatment of SCC-25 cells with an acute low-dose of 5, 25 cGy or 1 Gy gamma-rays given 60 min before a low-dose cisplatin challenge (0.1 and 1 microM for 1 h) resulted in a significant increase in resistance (p=0.2, 0.01 and <0.001 respectively). For pretreatment of SCC-25 cells with similar low-doses of gamma-rays 10 min before the challenge cisplatin dose, the increased resistance was reduced or absent and was only significantly increased for pretreatment with 25 cGy and a challenge cisplatin dose of 0.1 microM for 1 h (p = 0.02). Similar acute low-doses of y-rays given either 10 or 60 min after the challenge cisplatin dose did not increase resistance. CONCLUSIONS: The human squamous carcinoma cell line SCC-25 showed a low-dose hypersensitivity to cisplatin followed by increased resistance at higher doses. Treatment of SCC-25 cells with low-doses of gamma-rays can induce a protective effect to a subsequent low-dose cisplatin challenge.

High dose rate versus low dose rate brachytherapy for squamous cell carcinoma of the cervix: an economic analysis.

Brachytherapy is an established and important part of the management of invasive carcinoma of the cervix. Available evidence suggests that low dose rate (LDR) and high dose rate (HDR) are equivalent in terms of tumour control, adverse effects and survival. Proponents of outpatient HDR argue that it is less costly than LDR, but no economic evaluation has been published. We compared the costs of HDR and LDR (capital, operating, maintenance, source and operating costs) for Nucletron intracavitary equipment under alternative assumptions about the number of patients treated per year, the number of insertions per patient and discount rate. For example, for 3 HDR fractionations compared with 1 LDR fractionation, the LDR-3 (Nucletron) is the most cost-effective, practical machine for up to 40 patients per year. Although LDR-3 is more cost effective for a greater number of patients, HDR would be recommended for more than 40 patients a year for practical reasons. Similarly, for 5 HDR compared with 2 LDR fractionations, LDR-3 would be recommended for up to 20 patients per year and HDR for a greater number of patients. Recommendations for other HDR/LDR fractionations and annual number of patients seen can be derived from the model. This recommendation is based on no cost sharing with other sites. Cost sharing was beyond the scope of this analysis, though the principles are similar to the ones used. The model may be adapted to help equipment decision-making for a brachytherapy programme for an individual centre.

The relationship between the bladder and the cervix in patients undergoing intracavitary therapy.

Previous studies have shown a poor correlation between bladder damage and bladder dosage in patients treated with radiation therapy, including intracavitary therapy for uterine tumours. This study was undertaken to investigate prospectively the relationship between the cervical os and the bladder in patients undergoing intracavitary treatment. The computed tomography scans of 59 patients undergoing intracavitary treatment were analysed. The upper limit of the undistended bladder relative to the os extended from 5.5 cm cephalic to the cervix to 4.0 cm below it. The distance from the central tube to the posterior bladder wall at the level of the cervix ranged from 1.5 cm to 4.2 cm. This was positively associated with size of ovoid (p = 0.022), though with considerable individual variation. A separate analysis failed to show a consistent correlation with age or stage of disease. Thirty-nine of the 59 patients (65.5%) had asymmetrical bladders. Of these, half had "slight" asymmetry and the others had "marked" asymmetry. The thickness of the vesico-vaginal septum varied from 0.5 cm to 2.9 cm but was difficult to assess in some patients. In patients treated with medium-sized ovoids and those with Stage IB and IIB disease, the distance to the bladder base is greatest, though there is marked individual variation. These investigations reveal a marked variation in bladder position relative to the cervix in patients undergoing intracavitary therapy. The position of the bladder cannot be accurately predicted by any of these clinical criteria and requires to be defined by a radiological technique in the individual patient.

Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis.

PURPOSE: To evaluate the role of concurrent cisplatin plus radiotherapy in the treatment of cervical cancer. METHODS: A systematic review of randomized trials of cisplatin administered concurrently with external beam radiotherapy versus radiotherapy without cisplatin for cervical cancer was combined with a meta-analysis of results abstracted from published reports of the trials. RESULTS: Pooled survival rates from eight randomized trials that evaluated the role of cisplatin, alone or in combination with other chemotherapy agents, administered concurrently with external beam radiotherapy to patients with cervical cancer demonstrated a statistically significant effect in favour of cisplatin-based chemotherapy plus radiotherapy compared with radiotherapy without cisplatin (relative risk [RR] of death, 0.74; 95% confidence interval [CI], 0.64 to 0.86). The pooled RR of death among the six trials that enrolled only women with locally advanced cervical cancer was 0.78 (95% CI, 0.67 to 0.90). The pooled relative risk for the two trials in high-risk early-stage disease also demonstrated a statistically significant benefit for the addition of cisplatin-based chemotherapy to radiotherapy (RR=0.56; 95% CI, 0.41 to 0.77). CONCLUSION: This meta-analysis confirms that treatment with concurrent cisplatin-based chemotherapy plus radiotherapy improves overall survival over various controls in women with locally advanced cervical cancer, large stage IB tumours (prior to surgery) and high-risk early-stage disease (following surgery). The variation in control treatments and the quality of their delivery among the randomized trials makes interpretation difficult. Nonetheless, the meta-analysis supports the use of concurrent cisplatin with radical radiotherapy in the treatment of cervical cancer.

Surveillance programs for early stage non-seminomatous testicular cancer: a practice guideline.

BACKGROUND AND PURPOSE: To identify an appropriate surveillance program for men with clinical stage I non-seminomatous germ cell tumors of the testis (NSGCT). MATERIALS AND METHODS: A systematic review of the published literature was combined with a consensus process, around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. RESULTS: No randomized controlled trials (RCTs) comparing surveillance schedules were found, but data from 12 case series and one RCT which compared radiotherapy with surveillance were reviewed. Variations in the schedules were not associated with observed variations in relapse, salvage, or survival rates. CONCLUSIONS: Men with clinical stage I testicular cancer, as defined by a normal physical examination, normal radiological scans (computed tomography [CT]) and serum markers (alpha-fetoprotein [AFP] and beta-subunit of human chorionic gonadotropin (betaHCG) which are normal or fall within normal limits during their expected half-lives, are eligible for surveillance. A recommended surveillance schedule is as follows: 1) Physical examination, blood serum marker tests (AFP and HCG), and chest x-rays should be conducted every month in the first year, every 2 months in the second year, every 3 months in the third year, and every 6 months in the fourth and fifth years; and 2) CT scans of the abdomen and pelvis should be conducted every 3 months in the first year, every 4 to 6 months in the second year and every 6 months in the third year, and once a year in the fourth and fifth year.

Controversies in prostate cancer radiotherapy: consensus development.

The GU Radiation Oncologists of Canada (GUROC) had a consensus meeting in November 2000 to discuss and develop consensus on four controversial areas: risk assessment of localized prostate cancer, conformal radiotherapy, role of brachytherapy in prostate cancer and combined hormonal therapy and radiotherapy for prostate cancer. The meeting was a success and resulted in consensus being achieved on a number of areas. The group agreed on three risk groupings: low risk, intermediate risk and high risk localized prostate cancer based on clinical stage, Gleason score and PSA level. The participants agreed that based on available toxicity data from randomized controlled trials, conformal treatment techniques should be offered to patients receiving prostatic radiotherapy. Consensus was reached on the role of dose escalation in each of the three risk groups and is summarized in the article. At present there is insufficient evidence from randomized clinical trials to recommend the use of brachytherapy over current other standard therapy (radical prostatectomy or external beam radiotherapy). Non randomized published studies show promising short and intermediate term results. Where ever possible patients should be approached about participation in ongoing RCT's evaluating brachytherapy versus current other standard therapy. Outside a clinical trial the participants felt permanent seed implants should be considered an acceptable treatment option for appropriate patients with low risk prostate cancer. Based on randomized controlled trials the group agreed that patients with high risk disease should be treated with prolonged (up to 2-3 years) adjuvant hormonal therapy. Part of this hormonal treatment may be given in a neoadjuvant fashion. The group agreed that adjuvant hormones should not be routinely used in low and intermediate risk patients. Neoadjuvant hormones have been demonstrated to improve outcome in patients with bulky tumors. The role of neoadjuvant hormones in other patients with intermediate and low risk prostate cancer is unclear and will be clarified with the publication of recently completed studies. The consensus meeting strongly endorsed continued accrual to current studies investigating clinically relevant questions.

The use of CT for selectron patients.

Radiation-induced bladder and rectal complications are recognized complications of intracavitary therapy. In clinical studies the correlation between dose calculated and complications seen are inconsistent. The inconsistency is also present when utilizing the reference points recommended by the ICRU. We attempted to illustrate this inconsistency when looking at the bladder or rectum in intracavitary treatments. If reference points are inconsistent with maximum doses (which directly affect morbidity), their application is dubious.

Serodiagnosis of human cutaneous anthrax in India using an indirect anti-lethal factor IgG enzyme-linked immunosorbent assay.

Anthrax, caused by Bacillus anthracis, is primarily a zoonotic disease. Being a public health problem also in several developing countries, its early diagnosis is very important in human cases. In this study, we describe the use of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of anti-lethal factor (anti-LF) IgG in human serum samples. A panel of 203 human serum samples consisting of 50 samples from patients with confirmed cutaneous anthrax, 93 samples from healthy controls from areas of India where anthrax is nonendemic, 44 samples from controls from an area of India where anthrax is endemic, and 16 patients with a disease confirmed not to be anthrax were evaluated with an anti-LF ELISA. The combined mean anti-LF ELISA titer for the three control groups was 0.136 ELISA unit (EU), with a 95% confidence interval (CI) of 0.120 to 0.151 EU. The observed sensitivity and specificity of the ELISA were 100% (95% CI, 92.89 to 100%) and 97.39% (95% CI, 93.44 to 99.28%), respectively, at a cutoff value of 0.375 EU, as decided by receiver operating characteristic (ROC) curve analysis. The likelihood ratio was found to be 49.98. The positive predictive value (PPV), negative predictive value (NPV), efficiency, and Youden's index (J) for reliability of the assay were 92.5%, 100%, 98.02%, and 0.97, respectively. The false-positive predictive rate and false-negative predictive rate of the assay were 2.61% and 0%. The assay could be a very useful tool for early diagnosis of cutaneous anthrax cases, as antibodies against LF appear much earlier than those against other anthrax toxins in human serum samples.

High-intensity focused ultrasound for prostate cancer: a systematic review.

High-intensity focused ultrasound (HIFU) has recently been promoted as a non-invasive treatment option for prostate cancer. This systematic review sought to evaluate the evidence comparing it with standard treatment in patients with localised prostate cancer. The literature review included searches of MEDLINE, EMBASE, the Cochrane Library, annual meetings' abstracts and websites of evidence-based practice guideline producers. Studies were included if they were randomised controlled trials comparing HIFU with current management approaches, or were meta-analyses, systematic reviews or practice guidelines addressing HIFU. No randomised controlled trials or meta-analyses were identified. Seven systematic reviews and two practice guidelines were identified; neither contained randomised controlled trials. Adjusting the selection criteria to include case series found 34 clinical studies of HIFU. Twenty-nine evaluated HIFU as the primary treatment and five examined HIFU as salvage treatment for recurrence after radiotherapy. In most studies the outcomes used to determine efficacy were negative biopsy rates or prostate-specific antigen (PSA) levels. Among the 29 studies of HIFU as the primary treatment, negative biopsy rates ranged from 35 to 95% in 21 studies, a PSA nadir of ≤0.5 ng/ml ranged from 55 to 91% in 10 studies and mean PSA nadirs ranged from 0 to 1.9 ng/ml in 17 studies. Five studies reported 5-year disease-free survival rates ranging from 55 to 95%. Among five studies of HIFU as salvage treatment, negative biopsy rates ranged from 73 to 84% in four studies, a PSA nadir of ≤0.5 ng/ml ranged from 57 to 66% in three studies and mean PSA nadirs were 1.97 and 2.38 ng/ml in two studies, respectively. Current evidence on HIFU use in prostate cancer patients is of low quality, rendering it difficult to draw conclusions about its efficacy. Until results from case series are confirmed in prospective studies, the widespread use of HIFU is not supported.