The potential of Spirulina platensis to substitute antibiotics in Japanese quail diets: impacts on growth, carcass traits, antioxidant status, blood biochemical parameters, and cecal microorganisms.

The development of antibiotic-resistant microorganisms prompted the investigation of possible antibiotic substitutes. As a result, the purpose of the current study is to assess the effect of dietary Spirulina platensis extract as an antibiotic alternative on Japanese quail (Coturnix japonica) growth, antioxidant status, blood parameters, and cecal microorganisms. There was a total of 150 Japanese quails used in this study, divided equally among 5 experimental groups (10 birds per group with 3 replicates): group 1 (G1) received a basal diet without any S. platensis extract, group 2 (G2) received a basal diet supplemented with 1 mL S. platensis extract/kg, group 3 (G3) received a basal diet supplemented with 2 mL S. platensis extract/kg, group 4 (G4) received a basal diet supplemented with 3 mL S. platensis extract/kg, and group 5 (G5) received a basal diet supplemented with 4 mL S. platensis extract/kg from d 7 until d 35. The results showed that compared to the control birds in G1, Japanese quail supplemented with 4 mL of S. platensis extract/kg of diet (G5) had significantly better live body weight, body weight gain, feed intake, feed conversion ratio, digestive enzymes, blood parameters, liver and kidney functions, lipid profile, antioxidant profile, immunological parameters, and cecal microorganism's count. There were no significant changes in the percentage of carcasses, liver, and total giblets among all the 5 groups. Only gizzard percentage showed a significant increase in G2 compared to birds in G1. In addition, intestinal pH showed a significant drop in G2 and G5 compared to birds in G1. After cooking the quail meat, the juiciness and tenderness increased as S. platensis extract levels increased, whereas aroma and taste declined slightly as S. platensis extract levels increased. Furthermore, when a high concentration of S. platensis extract was used, the lightness of the meat reduced while its redness and yellowness increased. The disk diffusion assay showed that S. platensis extract had significant antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Campylobacter jejuni, and Salmonella typhi, with inhibition zones ranging from 16 to 42 mm. This activity may be attributable to the volatile chemicals in S. platensis extract, of which Geosmin and 2-methylisoborneol are the primary components. In the diet of Japanese quails, it is possible to draw the conclusion that the extract of S. platensis can be utilized as a feed additive and as an alternative to antibiotics.

A randomized phase III study of 72 h infusional versus bolus bleomycin in BEP (bleomycin, etoposide and cisplatin) chemotherapy to treat IGCCCG good prognosis metastatic germ cell tumours (TE-3).

BACKGROUND: Bleomycin is an integral part of combination chemotherapy in germ cell tumours. Pulmonary toxicity often necessitates drug cessation and death occurs in 1%-2% of patients. A continuous infusion of bleomycin might reduce lung toxicity when compared with the conventional weekly boluses given as part of standard BEP chemotherapy. PATIENTS AND METHODS: A phase 3 trial was conducted based on 212 men with IGCCCG good prognosis metastatic germ cell tumours with 1 : 1 randomization. They were stratified for age, smoking history and renal function. Patients received either conventional BEP with weekly bleomycin (30 000 units/week i.v. bolus) or as a 90 000 unit infusion on day 1 over 72 h. The primary endpoint was CT assessed lung toxicity, secondary endpoints included progression-free survival (PFS), changes in lung function testing and quality of life. Repeated measures mixed effects model was used to analyse the data. RESULTS: CT assessed lung toxicity for the infusional and conventional arm patients were respectively 80% versus 62% at the end of treatment and 54% versus 51% at 1-year post-treatment. There was no significant difference between the two arms for CT assessed lung toxicity (estimated regression coefficient = 1.4, 95% CI: -0.36, 3.16). Older patients had higher toxicity (coefficient = 4.81, 95% CI: 3.04, 6.58). Lung toxicity increased after 1 cycle and peaked at end of treatment (P ≤ 0.002) and then declined. Lung function testing did not predict for subsequent lung damage. The median follow-up was 2.5 years. Two-year PFS rate (infusional: 93%, conventional: 94%; hazard ratio =0.91, 95% CI: 0.33, 2.52) was similar. Cough (P = 0.002) but not shortness of breath (P ≥ 0.09) was associated with bleomycin toxicity. CONCLUSIONS: Infusional bleomycin has no advantage over standard administration. It supports abandoning routine pulmonary function testing, instead the presence of cough should be sought and the early use of CT scanning of the chest to evaluate potential lung toxicity is preferred.

Management of febrile neutropenia in an acute oncology service.

BACKGROUND: Neutropenic fever in patients receiving chemotherapy is a medical emergency and should be treated promptly within 1 h with antibiotics as specified within the 2009 NCAG report on chemotherapy services. AIM: To determine door-to-assessment, door-to-treatment and door-to-investigation intervals for patients with febrile neutropenia who presented to the inpatient Oncology Ward, the outpatient Oncology Day Unit and the Emergency Department in Addenbrooke's Hospital, Cambridge. DESIGN: Retrospective observational audit. METHODS: Thirty-two patients on treatment for solid cancers who were admitted with febrile neutropenia between January and December 2010 were identified, and paper and electronic medical records were analysed to determine door to: assessment, treatment and investigation intervals. RESULTS AND CONCLUSIONS: Patients in this series were assessed quicker and received the first dose of antibiotics faster when they presented to an oncology ward rather than the emergency department. However, imaging was performed faster and blood results issued quicker if performed in the emergency department due to a better infrastructure that has been tailored to comply with national targets. Nonetheless, compliance with optimum standards of care was poor, with only 9% of sampled patients getting antibiotics within 1 h of presenting to hospital, and 53% within 1 h of being assessed by a clinician.

Clinical examination does not assist in the detection of systemic relapse of testicular germ cell tumour.

AIMS: Patients on follow-up after orchidectomy or chemotherapy for testicular germ cell tumours follow a protocol of outpatient appointments and investigations designed to detect relapse. We wanted to investigate the contribution of clinical examination to patient management. MATERIALS AND METHODS: The notes of 70 consecutive patients who suffered a first systemic relapse of their germ cell tumour within the last 10 years were studied to determine how the relapse was detected. Second testicular tumours were excluded. RESULTS: Of the 69 patients whose notes were available, only one had a significant finding on physical examination, concurrent with abnormal markers. CONCLUSIONS: We suggest that, for patients following a planned programme of appointments and investigations, physical examination rarely contributes to the detection of systemic relapse in the follow-up of testicular germ cell tumours. It may therefore be possible to reconfigure follow-up to focus on investigations and telephone contact. We estimate that this change might be appropriate for 40% of attendances and might be welcomed by patients, many of whom find follow-up burdensome. If such a change were considered, patient education would be essential to ensure continuing compliance with the follow-up protocol.

Accelerated BEP: a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour.

BACKGROUND: We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. METHODS: Sixteen male patients with intermediate or poor prognosis metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day cycle for a planned relative dose-density of 1.5 compared with standard BEP. RESULTS: Eleven intermediate and five poor prognosis patients were treated. In all, 14 of 16 patients completed the study treatment. Toxicities were comparable to previous studies using standard BEP, except for mucositis and haematological toxicity that were more severe. The overall relative dose-density for all 16 patients was mean 1.38 (range 0.72-1.5; median 1.46). Complete response was achieved after chemotherapy alone in two patients (13%) and following chemotherapy plus surgery in nine additional patients (56%). Four patients (25%) had a partial response and normalised their marker levels. At a median follow-up of 4.4 years (range 2.1-6.8) the estimated 5-year progression-free survival probability is 81% (95% CI 64-100%). CONCLUSION: Accelerated BEP is tolerable without major additional toxicity. A randomised controlled trial will be required to obtain comparative efficacy data.

Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer.

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

Late relapse of stage i seminoma following single-agent carboplatin.

We present a case report of a patient who received adjuvant carboplatin for stage 1 seminoma and relapsed with abdominal lymph node metastasis at 48 months. In recent years, many oncologists have offered a single cycle of adjuvant carboplatin AUC7 as adjuvant treatment for stage 1 seminoma. The available data show a non-inferior relapse-free survival at 3 years compared with para-aortic radiotherapy. The rate of relapse beyond this point has not been reported. Patients with stage 1 seminoma represent a group of patients with excellent outcomes, and treatment options must also consider the late effects of treatment, of which there are increasing data of mortality for those treated with radiotherapy. Patients who opt for surveillance have a greater than 80% chance of remaining relapse free at 5 years, but those on surveillance require more CT examinations for follow-up. For those treated with single-agent carboplatin, our case report highlights that late relapse can occur, and we suggest that CT surveillance beyond 2 years is required given the lack of mature data on late relapse.

COX inhibitors and breast cancer.

There is considerable evidence to suggest that prostaglandins play an important role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX) catalyses the conversion of arachidonic acid to prostaglandins. In recent years, there has been interest in a possible role for COX inhibitors in the prevention and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Preclinical evidence favours an antitumour role for COX inhibitors in breast cancer. However, the epidemiological evidence for an association is conflicting. Trials are being conducted to study the use of COX inhibitors alone and in combination with other agents in the chemoprevention of breast cancer, and in the neo-adjuvant, adjuvant, and metastatic treatment settings. In evaluating the potential use of these agents particularly in cancer chemoprophylaxis, the safety profile is as important as their efficacy. Concern over the cardiovascular safety of both selective and nonselective COX-inhibitors has recently been highlighted.

The presentation and survival of patients with non-cutaneous AIDS-associated Kaposi's sarcoma.

BACKGROUND: Acquired immune deficiency syndrome related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe for the first time a proportion of patients with AIDS-KS who presented with no evidence of cutaneous disease. PATIENTS AND METHODS: From our cohort of 5932 individuals infected with the human immunodeficiency virus (HIV-1) treated in the HAART era, 319 were identified with KS. Of these, 11 patients (5.4%) were diagnosed with KS without the presence of any cutaneous disease. We compared their survival, clinical, immunological and virological characteristics to other individuals with KS. RESULTS: There were no statistically significant differences in survival, CD4 count or HIV viral load at KS presentation. We observed that tumour-associated oedema (P = 0.046) and non-oral gastrointestinal KS (P = 0.042) were significantly more common in patients with non-cutaneous KS. Only one case of non-cutaneous KS was observed prior to the era of highly active anti-retroviral therapy (HAART). CONCLUSIONS: Non-cutaneous KS is a recognisable condition; patients should be treated with the standard of care as their prognosis is not inferior. This is likely to reflect a strong immune response, in the era of HAART.

Managing metastatic prostate cancer.

Prostate cancer is one of the most commonly diagnosed malignancies in the west. Most patients with metastatic or recurrent prostate cancer initially respond to androgen deprivation therapy, but almost all eventually progress. This review will focus on current treatment options for metastatic prostate cancer, with a focus on hormonal therapies, chemotherapy and treatment of bony disease, along with biological and targeted therapy.

Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-alpha and the transcriptional repressor PLZF.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that acts to regulate gene expression by binding to palindromic DNA sequence, known as the estrogen response element, in promoters of estrogen-regulated genes. In breast cancer ERalpha plays a central role, where estrogen-regulated gene expression leads to tumor initiation, growth and survival. As an approach to silencing estrogen-regulated genes, we have studied the activities of a fusion protein between ERalpha and the promyelocytic leukemia zinc-finger (PLZF) protein, a transcriptional repressor that acts through chromatin remodeling. To do this, we have developed lines from the estrogen-responsive MCF-7 breast cancer cell line in which the expression of the fusion protein PLZF-ERalpha is conditionally regulated by tetracycline and shows that these feature long-term silencing of the expression of several well-characterized estrogen-regulated genes, namely pS2, cathepsin-D and the progesterone receptor. However, the estrogen-regulated growth of these cells is not inhibited unless PLZF-ERalpha expression is induced, an observation that we have confirmed both in vitro and in vivo. Taken together, these results show that PLZF-ERalpha is a potent repressor of estrogen-regulated gene expression and could be useful in distinguishing estrogen-regulated genes required for the growth of breast cancer cells.

Diet and prostate cancer.

There are four mini-reviews in this section, all on different areas of urological interest. Diet and prostate cancer continues to offer areas of clinical and laboratory research for investigation. Not every urologist looks after patients with spinal cord injury, but neuropathic bladder problems caused by other conditions are common. One of the acute conditions in these patients is autonomic dysreflexia, and this is covered here. I am about to introduce a series of papers which will form a consensus on the management of genitourinary trauma, which appears elsewhere in the journal. In this section this month, authors from Germany describe the diagnosis and treatment of male genital injuries. Finally, the concept that the urologists who operate on the largest volume of cases have the best outcomes from a particular operation is examined.