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Accessible summary What is known on the subject? 'Expertise by experience' has become an increasingly valued element of service design and delivery by mental health service providers., The extent and influence of mental health professionals' personal experience of mental ill health on clinical practice has seldom been interrogated in depth., What this paper adds to existing knowledge? We investigate how mental health nurses' own personal experience of mental ill health informs their mental health nursing practice with particular reference to direct work with service users., Participants said that personal experience could impact on work in three positive ways: to develop their relationship with service users, to enhance their understanding of service users and as a motivation for potential mental health nurses to join the profession., This study moves the discussion of the state of mental health nurses' mental health further towards the recovery and well-being focus of contemporary mental health care, where 'expertise by experience' is highly valued., What are the implications for practice? We must address the taboo of disclosure within clinical nursing practice and debate the extent to which personal and professional boundaries are negotiated during clinical encounters., Abstract Introduction 'Expertise by experience' is a highly valued element of service delivery in recovery-oriented mental health care, but is unacknowledged within the mental health nursing literature. Aim To explore the extent and influence of mental health professionals' personal experience of mental ill health on clinical practice. Method Twenty-seven mental health nurses with their own personal experience of mental ill health were interviewed about how their personal experience informed their mental health nursing practice, as part of a sequential mixed methods study. Results The influence of personal experience in nursing work was threefold: first, through overt disclosure; second, through the 'use of the self as a tool'; and third, through the formation of professional nursing identity. Discussion Mental health nurses' experience of mental illness was contextualized by other life experiences and by particular therapeutic relationships and clinical settings. In previous empirical studies, nurses have cited personal experience of mental illness as a motivator and an aspect of their identity. In this study, there was also an association between personal experience and enhanced nursing expertise. Implications for practice If drawing on personal experience is commonplace, then we must address the taboo of disclosure and debate the extent to which personal and professional boundaries are negotiated during clinical encounters. [ABSTRACT FROM AUTHOR]

The article offers information on initiation of 2007 amendments to Mental Health Act enabling nurses to become Approved Clinicians (AC), Responsible Clinicians (RC) and Approved Mental Health Professionals. Topics discussed include opportunities for patients and professionals; AC role being an opportunity for nurses to exercise powers and skills within legal framework; and RC should be an opportunity for the skillful exposition of senior nurses therapeutic skills.

Diet analyses and observations of cleaning behaviour of two cleaner fishes revealed that Labroides bicolor fed more on client mucus, but Labroides dimidiatus fed more on ectoparasites, and that L. bicolor interacted with fewer species (36 species) compared with L. dimidiatus (44 species). The client species which contributed most to the dissimilarity between cleaner species were the dusky farmerfish Stegastes nigricans and bicolor chromis Chromis margaritifer damselfishes, which L. dimidiatus interacted with more often than L. bicolor, and the striated Ctenochaetus striatus and brown Acanthurus nigrofuscus surgeonfishes, which L. bicolor interacted with more; L. bicolor interacted with all parrotfishes (Scaridae) more. These results confirm the importance of repeated interactions and partner choice in determining the nature of interactions in mutualisms. [ABSTRACT FROM AUTHOR]

Although studying the effects of diet on cognitive function in children is of great interest to nutritionists, many have not received the formal training in the principles and practice of assessment necessary to properly evaluate research studies or to design and conduct research themselves. This paper is aimed at such an audience and assumes little prior knowledge of the field. A short description of neural development in childhood is followed by a discussion of important principles of assessment. A level of assessment approach is used to present a selection of widely used cognitive tests organized by cognitive domain and age group. Practical information about the tests is presented in tabular form and a list of useful websites is included. [ABSTRACT FROM AUTHOR]

Objective To determine the incidence and clinical correlates of postoperative cardiac arrhythmias in patients undergoing elective large bowel resection. Methods Fifty-one consecutive patients undergoing elective open colorectal resection were recruited for this prospective observational study. Participating patients underwent daily three-lead electrocardiograms postoperatively. Data regarding potential risk factors for arrhythmias were recorded. Post-operative complications were recorded. Results Thirteen (26%) patients developed a postoperative arrhythmia, most commonly atrial fibrillation. Significant univariate correlates with postoperative arrhythmias were: age ( P < 0.01), hypertension ( P < 0.01), pre-operative serum potassium levels ( P < 0.01), postoperative pulmonary oedema ( P = 0.03), postoperative serum potassium ( P = 0.03) and sodium ( P < 0.01). Arrhythmia patients were more likely to have other complications ( P = 0.02). Thirty-one percent of arrhythmia patients had underlying sepsis compared with 18% of controls ( P = 0.38). Conclusion Arrhythmias are common following elective large bowel resection. They occur in older patients and are associated with the development of other complications. [ABSTRACT FROM AUTHOR]

Focuses on the use of a KTP laser fine fenestra stapedotomy in the surgical management of otosclerosis. Background on the evolution of the stapedectomy operation; Discussion on the experience of stapedial surgery for otosclerosis; Details on the technique of laser fine fenestra stapedotomy with vein graft interposition.

(1) A 5-year survey of the oat crown rust and oat stem rust pathogens (P. coronata and P. graminis avenae) in New South Wales, found considerable annual variation in the abundance, racial diversity and virulence of both pathogen populations. (2) The racial diversity of both pathogens was significantly greater in the northern than the southern half of the State. (3) On average, isolates of P. coronata and P. graminis avenae from northern New South Wales were, respectively, 22.4 and 175% more virulent than those from the south. However, these differences were not statistically significant. (4) The relative importance of cultivated and wild oats as hosts to the two pathogens is assessed. (5) The implications of these results for an understanding of host--pathogen co-evolutionary interactions is discussed. [ABSTRACT FROM AUTHOR]

(1) Twenty-one populations of wild oats collected throughout New South Wales were assessed at the seedling stage for their reaction to four races of the oat crown rust pathogen (Puccinia coronata) and four races of the oat stem rust pathogen (P. graminis avenae). (2) Populations from northern New South Wales were significantly more resistant and more diverse in their infection response to P. coronata than were populations from southern New South Wales. (3) Differences in the distribution of resistance to P. graminis avenae were considerably less marked. For populations of A. fatua there was a non-significant increase in resistance in the north. For populations of A. barbara, on the other hand, there was no difference in the average level of resistance between northern and southern populations. (4) No differences were detected in the average response of populations of any of the three wild oat species to infection by P. coronata. For P. graminis avenae this was also true for populations from the north of the State. (5) The importance of intra-population diversity in infection response as a means of reducing disease is discussed. [ABSTRACT FROM AUTHOR]

Follicular lymphoma is a B cell malignancy prone to transformation into a large cell diffuse histology. This progression may be multi-clonal as determined by IgH rearrangement. Similar multi-clonal occurrences have been described in immunocompromised patients. However, the lymphoma cells remain predominantly of B cell type. Rarely, composite lymphomas with diffuse T cell histology have been reported arising from follicular lymphoma. The development of T cell leukaemia in a patient with a pre-existing B cell malignancy is an extremely rare event. The occurrence of T cell acute lymphoblastic leukaemia (T-ALL) following follicular lymphoma (FL) has not previously been reported. We report a case of Philadelphia positive (Ph+) T cell ALL developing in a patient who previously had FL which may give some insight into the cell of origin and the defects responsible for malignant transformation of the lymphocytes. Bone Marrow Transplantation (2000) 26, 1113–1115. [ABSTRACT FROM AUTHOR]

The article offers information on mental health nursing. The giving of the self in mental health nursing is possibly most skilful when the nurse needs to move between care and control, when empathy and compassion are affected by the coercive elements of psychiatric care. A study of nurses with personal experience of mental health problems in this issue is also discussed.

The article presents a letter to the editor responding to a comment on the study about urinary markers in lupus nephritis.

The article presents the abstract of the paper "Insights from Genetic, Remotely Sensed, and Demographic Data for the Conservation of the Critically Endangered Cross River Gorilla (Gorilla Gorilla Diehli)," by R.A. Bergl and colleagues to be presented at the 21st Congress of the International Primatological Society in Entebbe, Uganda from June 25-30, 2006.

Purpose To prospectively assess the subjective experience of patients and the degree of benefit they felt they gained from attending the Multidisciplinary Head and Neck Clinic (MDHNC). Methodology An internally validated questionnaire of patient responses to their experiences at the MDHNC was implemented prospectively. Data were gathered between May and September 2006. The questionnaire consisted of 36 questions, addressing 3 components of the clinic; before, during and after attendance. Twenty four of 48 questionnaires were completed. Results Patients’ experiences of the clinic were mainly positive. All patients reported feeling adequately informed about both illness and their treatment options. No patients left with unanswered questions. All, but one patient, tolerated the examination well, although 4 patients were unprepared for the number of people present at the clinic. Twenty two patients especially valued the post-clinic discussion with their specialist. Five patients felt that insufficient information about treatment choice was provided to their family. No discrepancy between internal validation questions was recorded. Conclusion Patients expressed a high level of appreciation for the care provided in the multidisciplinary clinic. Contrary to our expectations, patients generally did not mind examination in the presence of a large number of clinicians. Most patients reported particularly valuing the discussion with the treating specialist after the clinic visit. Reducing waiting times, providing clearly written plans for treatment resulting from the clinic, and distributing more information to assist individuals accompanying patients, emerged as target areas for future improvement. [ABSTRACT FROM AUTHOR]

The article presents a clinical diagnosis of an 81-year-old man with a 2-month history of diplopia and recent onset of left-sided ptosis. The patient also experience pain in the left eye and left nasal congestion. In this context, the fullness of the left orbit and left ptosis and restriction of left eye movements in all directions were observed.

Background: There is a need in primary care for an easily administered instrument to give early indications of disorders in mother-infant relationships. Methods: An 84 item questionnaire was administered to 104 subjects, including normal mothers, depressed mothers with a normal mother-infant relationship and mothers with bonding disorders. A principle component analysis was used to select items for scale construction. Scale scores were compared with interview data. Reliability, sensitivity and specificity of the scales were measured. Findings: 4 factors of clinical relevance were obtained and used to construct 4 scales. The questionnaire was reduced to 25 questions. Scale 1 (impaired bonding) had a sensitivity of 0.93 in detecting mothers with bonding disorder. Scale 2 (rejection and anger) specifically identified mothers with severe disorders. Scale 3 may be useful in anxious mothers. Scale 4 signalled the presence of incipient abuse, requiring urgent intervention. Interpretation: This questionnaire can be used, with the Edinburgh Postnatal Depression Scale, by midwives and health visitors, for the early diagnosis of mother-infant bonding disorders. [ABSTRACT FROM AUTHOR]

Background Many measures of infants' early cognitive development, including the BSID-II (The Bayley Scales of Infant Development), mix together test items that assess a number of different developmental domains including language, attention, motor functioning and social abilities, and some items contribute to the assessment of more than one domain. Consequently, the scales may lead to under- or over-estimates of cognitive abilities in some clinical samples and may not be the best measure to use for matching purposes. Method To address this issue we created a modified form of the BSID-II (the BSID-M) to provide a ‘purer’ assessment of the general cognitive capacities in infants with Down syndrome (DS) from 6 to 18 months of age. We excluded a number of items that implicated language, motor, attentional and social functioning from the original measure. This modified form was administered to 17 infants with Down syndrome when 6, 12 and 18 months old and to 41 typically developing infants at 4, 7 and 10 months old. Results The results suggested that the modified form continued to provide a meaningful and stable measure of cognitive functioning and revealed that DS infants may score marginally higher in terms of general cognitive abilities when using this modified form than they might when using the standard BSID-II scales. Conclusions This modified form may be useful for researchers who need a ‘purer’ measure with which to match infants with DS and other infants with intellectual disabilities on cognitive functioning. [ABSTRACT FROM AUTHOR]

Objective: Immediate facial nerve reconstruction is the standard of care following radical parotidectomy; however, quality of life comparisons with those undergoing limited superficial parotidectomy without facial nerve sacrifice is lacking. Method: Patients who underwent parotidectomy were contacted to determine quality of life using the University of Washington Quality of Life and Parotidectomy Specific Quality of Life questionnaires. A total of 29 patients (15 in the radical parotidectomy and 14 in the limited superficial parotidectomy groups) completed and returned questionnaires. Results: Using the University of Washington Quality of Life Questionnaire, similar quality of life was noted in both groups, with the radical parotidectomy group having significantly worse speech and taste scores. Using the Parotidectomy Specific Quality of Life Questionnaire, the radical parotidectomy group reported significantly worse speech, eye symptoms and eating issues. Conclusion: Those undergoing radical parotidectomy with reconstruction had comparable overall quality of life with the limited superficial parotidectomy group. The Parotidectomy Specific Quality of Life Questionnaire better identified subtle quality of life complaints. Eye and oral symptoms remain problematic, necessitating better rehabilitation and more focused reconstructive efforts. [ABSTRACT FROM AUTHOR]

Men with low serum prostate-specific antigen (PSA) and high Gleason grade group (GGG) are thought to have poor outcomes compared to high PSA secretors. However, there is limited outcome data to support this. We report clinical outcomes from a single-institutional cohort of men presenting with locally advanced prostate cancer but low serum PSA. Data from electronic database of a UK tertiary cancer center was acquired for men with histological diagnosis of prostate adenocarcinoma, GGG 4 or 5, stage ≥cT3a, and PSA <10ug/L at diagnosis. Men with metastatic disease, or prior androgen deprivation therapy (ADT) were excluded. Biochemical progression was defined as per Phoenix criteria (PSA > nadir+2) for primary radiotherapy, or PSA >0.2 ug/L after primary prostatectomy (and post-operative radiotherapy, if received). Overall survival (OS, from date of diagnosis to death), metastasis-free survival (MFS, from diagnosis to first recorded metastasis or death), and biochemical progression free survival (bPFS, from diagnosis to biochemical progression or death) were estimated by Kaplan Meier method, and multivariable analysis performed using Cox proportional hazards method. Medical records of 7,200 men presenting with non-metastatic prostate cancer from 2013 to 2021 were screened, of which 270 men satisfying the eligibility criteria were included for this study. Initial analysis of 123 men shows median PSA at presentation 7.1 ug/L (IQR 5.6-8.5), and median age 70 years (IQR 65-75). Histology was GGG 4 in 47.6% and 5 in 52.4%. Tumor stage was cT3a in 56.6%, cT3b in 36.9%, and T4 in 6.6%. Pelvic nodes were involved in 5% patients. Majority (83.7%) were treated with radical radiotherapy (external beam alone 64.2%, brachytherapy boost 19.5%), with 24 months ADT; 11.4% underwent radical prostatectomy, and 4.9% received ADT alone. Three men (2.4%) received docetaxel, and one received abiraterone. At a median follow up of 66 months (IQR 27-77), 36 (29.3%) patients had biochemical failure. Total 23 (18.6%) patients had metastases at recurrence, which were visceral in 4%, bone-only in 10%, and nodal-only in 4%. Total 38 (30.6%) patients had died, 23% with prostate cancer and 11% due to other causes. Five-year bPFS was 65.9%, MFS 69.0%, and OS was 77.4%. GGG 5 (versus 4) was associated with significantly worse 5-year bPFS (59.4% vs 73.9%, HR 1.8, 95% CI 1.0-3.2, p = 0.05) and MFS (59.2% vs 81.6%, HR 2.2, 1.2-4.2, p = 0.02). On multivariable analysis including age and PSA at diagnosis, only GGG 5 was associated with worse bPFS (HR 1.8, 1.0-3.3, p = 0.05) and MFS (HR 2.42, 1.25-4.67, p = 0.009). Men with low secreting but high Gleason grade group prostate cancer are a relatively rare group with poor clinical outcomes despite being non-metastatic. Ongoing work (expected completion June 2023) will analyze remaining cases, and compare outcomes within an expanded multicentric cohort with matched controls having elevated PSA at presentation. [ABSTRACT FROM AUTHOR]

Objective: The Peer Approaches to Lupus Self-management (PALS) program was developed as a peer mentoring tool to improve health behaviors, beliefs, and outcomes in African American women with systemic lupus erythematosus (SLE). This study aims to assess the cost of the PALS intervention and determine its effectiveness when compared to existing treatments. Methods: Peer mentors and mentees were paired on shared criteria such as life stage, marital status, or whether they were mothers. This 12-week program consisted of a weekly peer mentoring session by telephone. Cost of healthcare utilization was evaluated by assessing the healthcare costs pre- and post-intervention. Validated measures of quality of life, self-management, disease activity, depression, and anxiety were collected. Total direct program costs per participant were totaled and used to determine average per unit improvement in outcome measures. The benefit-cost ratio and pre- versus post-intervention hospital charges were examined. Results: A total of 20 mentees and 7 mentors were enrolled in the PALS program. All PALS pairs completed 12 sessions lasting an average of 54 minutes. Mentees reported statistically significant decreases in patient-reported disease activity, depression, and anxiety, with improved trends in patient activation or patient engagement in their disease and management. The total cost per patient was $1291.50, which was $107.62 per patient per week. There was a savings of $23,417 per individual receiving the intervention with a benefit-cost ratio of 18.13 per patient. Conclusion: These findings suggest that the PALS intervention was effective in improving patient-level factors and was cost-effective. Future research will need to validate these findings in a larger sample. [ABSTRACT FROM AUTHOR]

Background: EXPERT and EXPERT-C were phase II clinical trials of neoadjuvant chemotherapy (NACT) followed by chemoradiotherapy (CRT) in high-risk, locally advanced rectal cancer (LARC). Design: We pooled individual patient data from these trials. The primary objective was overall survival (OS) in the intention-to-treat (ITT) population. Prognostic factors were also analysed. Results: A total of 269 patients were included. Of these, 91.1% completed NACT, 88.1% completed CRT and 240 (89.2%) underwent curative surgery (R0/R1). After a median follow-up of 71.9 months, 5-year progression-free survival (PFS) and OS were 66.4% and 73.3%, respectively. In the group of R0/R1 resection patients, 5-year relapse-free survival (RFS) and OS were 71.6% and 77.2%, respectively, with local recurrence occurring in 5.5% and distant metastases in 20.6% of cases. Significant prognostic factors after multivariate analyses included age, tumour grade and MRI extramural venous invasion (mrEMVI) at baseline, MRI tumour regression grade (mrTRG) after CRT, ypT stage after surgery and adherence to study treatment. mrTRG after NACT was associated with PFS (P = 0.002) and OS (P = 0.018) and appeared to stratify patients based on the incremental benefit from sequential CRT. Among the outcome measures considered, in the subgroup of R0/R1 resection patients, ypT and ypStage had the highest predictive accuracy for RFS (concordance index: 0.6238 and 0.6252, respectively) and OS (concordance index: 0.6094 and 0.6132, respectively). Conclusions: Administering NACT before CRT could be a potential strategy for high-risk LARC. In this setting, mrTRG after CRT is an independent prognostic factor, while mrTRG after NACT should be tested as a parameter for treatment selection in trials of NACT ± CRT. ypT stage may be a valuable surrogate end point for future phase II trials investigating intensified neoadjuvant treatments in similar patient populations. [ABSTRACT FROM AUTHOR]

Background While voice is integral to sports coaching, currently there is a dearth of research considering coaches' occupational vocal health. Objective To investigate football coaches' occupational voice use and vocal health (including the role of voice in coaching and the identification and management of workplace risk factors). Design A mixed-methodological approach (interviews, a questionnaire and acoustic voice measurement) using descriptive statistics and thematic analyses. Setting On-site at three Australian Football League clubs and one Australian Super 14's Rugby Union club. Participants 12 male coaches volunteered to participate. Inclusion criteria required participants to be employed full time as elite level football coaches. Results Participants perceived their voices as crucial for the frequent verbal communication required while coaching. Acoustic measurements revealed that, across work contexts, participants engaged in heavy vocal loads. Coaches also identified various aspects of their physical and organisational environments that impacted negatively on their voices. These vocal demands appear to be associated with negative health consequences. All participants reported experiencing voice symptoms (such as vocal fatigue and hoarseness) at least some of the time while coaching. Coaches suggested several strategies that reduced these symptoms, but were generally unaware of why these assisted their voices. Furthermore, coaches did not actively contemplate how to address risk factors or promote positive vocal health experiences at work. Conclusion This study demonstrates the critical reliance coaches have on their voices. It also suggests that the nature of vocal demands and workplace environments may negatively impact on coaches' vocal health. While participants demonstrated some insight into their voice use, this did not necessarily translate to awareness of vocal health or management of risk factors. A greater understanding of risk factors and their management is required to better support the occupational vocal health of coaches. [ABSTRACT FROM PUBLISHER]

The level of glutamine (Gln) deamidation in bone collagen provides information on the diagenetic history of bone but, in order to accurately assess the extent of Gln deamidation, it is important to minimise the conditions that may induce deamidation during the sample preparation. Here we report the results of a preliminary investigation of the variability in glutamine deamidation levels in an archaeological bone due to: a) sampling location within a bone; b) localised diagenesis; and c) sample preparation methods. We then investigate the effects of pre-treatment on three bone samples: one modern, one Medieval and one Pleistocene. The treatment of bone with acidic solutions was found to both induce deamidation and break down the collagen fibril structure. This is particularly evident in the Pleistocene material (∼80,000 years BP) considered in this study. We show that ethylenediaminetetraacetic acid (EDTA), when used as an alternative to hydrochloric acid (HCl) demineralisation, induces minimal levels of deamidation and maintains the collagen fibril structure. Areas of bone exhibiting localised degradation are shown to be correlated with an increase in the levels of Gln deamidation. This indicates that the extent of Gln deamidation could provide a marker for diagenesis but that sampling is important, and that, whenever possible, subsamples should be taken from areas of the bone that are visually representative of the bone as a whole. Although validation of our observations will require analysis of a larger sample set, deamidation measurements could be a valuable screening tool to evaluate the suitability of bone for further destructive collagen analyses such as isotopic or DNA analysis, as well as assessing the overall preservation of bone material at a site. The measure of bone preservation may be useful to help conservators identify bones that may require special long-term storage conditions. [ABSTRACT FROM AUTHOR]

Background: The REAL-2 trial demonstrated that capecitabine and oxaliplatin were effective alternatives to fluorouracil and cisplatin, respectively, when used in triplet chemotherapy regimens for previously untreated oesophago-gastric cancer. The aim of the current analysis was to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in the REAL-2 cohort. Material and methods: A post hoc exploratory analysis was carried out on REAL-2 patients with the available absolute neutrophil count and absolute lymphocyte count. A high NLR was defined using a cut-off value of >3.0. The NLR was then correlated with clinical outcomes including overall survival (OS), progression-free survival (PFS) and objective response rate. Survival curves were generated using the Kaplan-Meier method and comparison between groups was carried out using Cox regression. Results: Data were available in 908 of the 1002 REAL-2 participants. Of these, 516 (56.8%) were deemed to have a high NLR. In univariate analysis, high NLR was associated with a hazard ratio (HR) for OS of 1.73 (1.50-2.00), P < 0.001, compared with low NLR, equating to median OS values of 9.1 [95% confidence interval (CI) 8.0-9.6] and 12.7 months (95% CI 10.8-14.4), respectively. The NLR remained highly significant for OS (P < 0.001) in a multivariate model including performance status, age, disease extent, presence of liver metastases and presence of peritoneal metastases. For PFS, high NLR was associated with an HR of 1.63 (1.41-1.87), P < 0.001, compared with low NLR in univariate analysis. No significant interaction was found between NLR status and treatment arm, 13% of all patients with low NLR achieving survival beyond 24 months compared with only 6% of patients with high NLR (P < 0.001). Conclusion: Our results confirm that high NLR status had a significant negative prognostic effect in the REAL-2 trial population. Based on the multivariate analysis, this effect was independent of other known prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. Patients and methods: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNAwas isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). Conclusion: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit. [ABSTRACT FROM AUTHOR]

Abstract: Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial. Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed. Results: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n =40; CAPOX-C, n =38). In this population, after a median follow-up of 63.8months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p =0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p =0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p =0.20). Conclusions: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted. [Copyright &y& Elsevier]

Abstract: Background: Preclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (GemCap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer. Patients and methods: In a phase II expansion cohort, patients with chemonaive locally advanced or metastatic pancreatic cancer received gemcitabine (1000mg/m2 D1, 8, 15), capecitabine (1400mg/m2 D1–21), erlotinib (100mg daily) and bevacizumab (5mg/kg D1, 15) every 28days. The primary endpoint was radiological response rate by response evaluation criteria in solid tumours (RECIST). Computed tomography (CT) assessment was performed every 8weeks. Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment. Results: In total 44 patients (phases I & II) were recruited. The median cycles delivered were 6 (range 1–16). Confirmed radiological responses were seen in 23% (95% confidence interval (CI): 11–38%) of patients. The median progression-free and overall survival for the entire cohort was 8.4 and 12.6months, respectively. In patients with metastatic disease the median overall survival was 10.1months. Common grade 3/4 toxicities were; neutropenia 52%, lethargy 32%, diarrhoea 18% and hand-foot syndrome 18%. Conclusion: The combination of gemcitabine, capecitabine, erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population. [Copyright &y& Elsevier]

We have investigated the microstructure and bonding of two biomass-based porous carbon chromatographic stationary phase materials (alginic acid-derived Starbon® and calcium alginate-derived mesoporous carbon spheres (AMCS)) and a commercial porous graphitic carbon (PGC), using high resolution transmission electron microscopy, electron energy loss spectroscopy (EELS), N2 porosimetry and X-ray photoelectron spectroscopy (XPS). The planar carbon sp 2-content of all three material types is similar to that of traditional non-graphitizing carbon although, both biomass-based carbon types contain a greater percentage of fullerene character (i.e. curved graphene sheets) than a non-graphitizing carbon pyrolyzed at the same temperature. This is thought to arise during the pyrolytic breakdown of hexauronic acid residues into C5 intermediates. Energy dispersive X-ray and XPS analysis reveals a homogeneous distribution of calcium in the AMCS and a calcium catalysis mechanism is discussed. That both Starbon® and AMCS, with high-fullerene character, show chromatographic properties similar to those of a commercial PGC material with extended graphitic stacks, suggests that, for separations at the molecular level, curved fullerene-like and planar graphitic sheets are equivalent in PGC chromatography. In addition, variation in the number of graphitic layers suggests that stack depth has minimal effect on the retention mechanism in PGC chromatography. [ABSTRACT FROM AUTHOR]

Background HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial. Patients and methods Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0–3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio ≥2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed. Results Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated±cetuximab. Conclusions Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation. [ABSTRACT FROM PUBLISHER]

Background: Targeting platelet-derived growth factor receptor-β (PDGFR-β) is a potential strategy to reduce tumour-related interstitial fluid pressure, enhance cytotoxic drug uptake and reduce chemoresistance. This study aimed to define safe doses of gemcitabine plus oxaliplatin when combined with imatinib (potent PDGFR-β inhibitor) in patients with advanced gemcitabine-refractory pancreatic cancer (PC). Patients and methods: Using a 3 + 3 dose escalation design, patients of performance status zero or one were entered into five sequential dose levels (DLs) of gemcitabine [day 1, from 400 (DL1) to 1000 mg/m2 (DL4)] and oxaliplatin [day 2, 85 (DL1–4) and 100 mg/m2 (DL5)] two weekly. Imatinib 400 mg od was given for 7 days (day minus 2–5) each cycle. Results: Twenty-seven patients received 168 cycles in total. Median age was 61 years (44–74 years). Dose-limiting toxicities occurred in two of two patients at DL5 (G4 thrombocytopenia, G3 lethargy), defined as the maximum tolerated dose and one of six patients at DL4 (G3 lethargy). DL4 was expanded. There were 2 of 27 partial responses and 14 of 27 stable disease [disease control 52%, 95% confidence interval (CI) 32% to 71%]. Median progression-free survival and overall survival were 4.6 (95% CI 2.1–7.0) and 5.6 months (95% CI 2.5–8.7), respectively. Conclusion: In gemcitabine-refractory PC, gemcitabine (1000 mg/m2) and oxaliplatin (85 mg/m2) can be safely combined with imatinib given on a 7 days on and 7 days off intermittent schedule. [ABSTRACT FROM PUBLISHER]

Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent 'substrate-selective inhibitors' of endocannabinoid oxygenation. Crystal structures of the COX-2-(R)-naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R) enantiomers relative to (S) enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion (DRG) cells. Substrate-selective inhibition provides new tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin, cisplatin and capecitabine (ECX) chemotherapy in untreated advanced oesophago-gastric (OG) cancer. The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone.Patients and methods: In this multicentre, randomised open-label phase II study, 72 patients with metastatic OG cancer were randomly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m2, cisplatin 60 mg/m2 on day 1 and capecitabine 1250 mg/m2 daily in a 21-day cycle (ECX) or the same ECX regimen alone. The primary end point was objective response. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life, safety and tolerability.Results: Following random assignment, 35 patients (median age 59 years) received ECX/matuzumab and 36 patients (median age 64 years) ECX. The addition of matuzumab to ECX did not improve objective response: 31% for ECX/matuzumab [95% confidence interval (CI) 17–49] compared with 58% for the ECX arm (95% CI 41–74) P = 0.994 (one sided). There was no significant difference in median PFS: 4.8 months (95% CI 2.9–8.1) for ECX/matuzumab versus 7.1 months (95% CI 4.4–8.5) for ECX, or in median OS: 9.4 months (95% CI 7.5–16.2), compared with 12.2 months (95% CI 9.8–13.8 months). Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups, respectively.Conclusion: Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer. Therefore, ECX/matuzumab should not be examined further in phase III trials. [ABSTRACT FROM PUBLISHER]

Background: The Follicular Lymphoma International Prognostic Index (FLIPI) allows physicians to stratify patients into groups with distinct prognoses, however its ability to predict the treatment efficacy has not been fully investigated. The aim of this study was to validate on this respect the FLIPI system in an independent cohort and compare it with the International Prognostic Index (IPI) used for aggressive lymphomas. Methods: Records from patients referred to our unit with a diagnosis of follicular lymphoma (FL) were retrospectively reviewed. Data required for FLIPI and IPI scores were collected along with data regarding first-line chemotherapy and time to treatment failure (TTF) and overall survival (OS). Results: Of 162 patients screened, 130 were assessable for both (FLIPI and IPI) scores. OS for low-risk (LR) patients identified either with IPI or FLIPI was significantly longer compared to intermediate-risk (IR) and high-risk (HR) groups, with FLIPI allowing a more even patient distribution among the risk groups. For patients receiving first-line chemotherapy within 6 months of diagnosis, a low FLIPI score was associated with a longer TTF (3-year TTF rates: 68.0, 33.7 and 31.0% for FLIPI-defined LR, IR and HR patients, respectively, p = 0.026). Conclusion: Our data support the prognostic value of both IPI and FLIPI, with FLIPI demonstrating a more convenient patient distribution among risk classes. A low FLIPI score was also associated with a longer TTF. This might partially contribute to a more favourable prognosis. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There is no standard second line therapy for relapsed oesophago-gastric (O-G) cancer. We recruited 29 eligible patients with relapsed O-G cancer who had progressed during or within 3 months of prior chemotherapy to assess the efficacy and toxicity of capecitabine [2,000 mg/(m2 day) on days 1–14] and irinotecan (250 mg/m2) given every 3 weeks. Five patients (17%) demonstrated objective response, while a further seven patients (24%) achieved disease stabilisation. Median progression-free survival and overall survival were 3.1 months (95% CI = 2.2–4.1 months) and 6.5 months (95%CI = 6–7.1 months), respectively. Among symptomatic patients, palliation of tumour-related symptoms included resolution of reflux (5/12 pts), dysphagia (3/9 pts) and weight loss (4/9 pts), improvements in anorexia (4/10 pts), nausea (3/4 pts), vomiting (4/6 pts) and pain (4/16 pts). Grade 3–4 toxicities were diarrhoea (15%), nausea and vomiting (7%), lethargy (31%), neutropenia (31%), anemia (14%) and thrombocytopenia (7%). Capecitabine and irinotecan has anti-tumour activity as second line treatment for relapsed O-G cancer, and provides an important improvement in disease related symptoms. [ABSTRACT FROM AUTHOR]

Preoperative cisplatin/fluorouracil is used for the treatment of localised oesophageal carcinoma. This phase II study aimed to assess the efficacy and safety of administering preoperative epirubicin/cisplatin/capecitabine (ECX). Patients with stage II or III oesophageal/gastro-oesophageal junctional adenocarcinoma from one institution received 4 cycles of ECX (epirubicin 50 mg m−2 day 1, cisplatin 60 mg m−2 day 1, capecitabine 625 mg m−2 b.i.d. daily) followed by surgery. The primary end point was the pathological complete response (pCR) rate based on a Simon two-stage design. Secondary end points included overall and progression-free survival (OS/PFS). Thirty-four patients were recruited: median age 60 years (range 41–81), 91% male, 97% PS 0/1, 80% T3, 68% N1. Thirty-one patients completed four ECX cycles. Grade 3/4 toxicities 5% included neutropenia (62%), hand–foot syndrome (15%) and nausea/vomiting (9%). Thirteen out of 28 (46%) evaluable patients responded to chemotherapy by EUS (30% reduction in maximal tumour thickness). Twenty-six out of 34 (76%) patients underwent resection (R0=73%, R1=27%). Post-operatively, two patients died within 60 days of surgery. The pCR rate was 5.9% (95% CI 0–14%) in the intent-to-treat population. According to the statistical design, this prompted early study termination. However, with a median follow-up of 34 months the median OS and 1- and 2-year survival rates were 17 months, 67 and 39% respectively. Median PFS was 13 months. Of the 14 relapsed patients, 10 presented with distant metastases. Preoperative ECX is feasible and well tolerated. Although associated with a low pCR rate, survival with ECX was comparable with published studies suggesting that pCR may not correlate with satisfactory outcome from preoperative chemotherapy for localised oesophageal adenocarcinoma.British Journal of Cancer (2009) 100, 1725–1730; doi:10.1038/sj.bjc.6605070 www.bjcancer.com Published online 12 May 2009 [ABSTRACT FROM AUTHOR]

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m(-2), cisplatin 60 mg m(-2) on day 1 and capecitabine 1000 mg m(-2) daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43-82), disease stabilisation of 25% (95% CI: 11-47) and a disease control rate (CR + PR + SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3. [ABSTRACT FROM AUTHOR]

The World Health Organisation (WHO) classification (2000) is widely used to classify neuroendocrine carcinomas (NECs), yet its prognostic value needs to be confirmed. In this study, patients with metastatic NECs (n=119) were classified according to WHO guidelines into well differentiated and poorly differentiated (WDNECs and PDNECs). Histological differentiation based on WHO criteria had the highest impact on overall survival (OS) (PDNECs : WDNECs hazard ratio (HR)=4.02, P=0.02); however, PDNECs represented only a small percentage of patients (8%). In a WDNEC-restricted analysis, abnormal liver function tests (LFTs) and elevated urinary 5-hydroxyindoleacetic acid (u5HIAA) were independent prognostic factors for survival (HR=2.65, P=0.006 and HR=2.51, P=0.003, respectively) and were used to create a WDNEC-specific prognostic model (low risk=both normal, intermediate risk=one of them abnormal, high risk=both abnormal). Low-risk WDNECs had the most favourable prognosis (median OS, mOS 8.1 years), which was significantly better compared to both intermediate-risk and high-risk WDNECs (mOS 3.2 and 1.4 years, with P=0.01 and P<0.001, respectively). High-risk WDNECs displayed the shortest OS (1.3 years), which was similar to that of PDNECs (P=0.572). This analysis supports the prognostic value of WHO classification for metastatic NECs arising from the gastroenteropancreatic tract; however, risk stratification using readily available u5HIAA and LFTs may be necessary for the heterogeneous group of WDNECs. [ABSTRACT FROM AUTHOR]

In a multivariate analysis of 154 patients receiving chemotherapy, baseline CA19-9 was an independent prognostic factor for overall survival (OS) (HR 1.8; 95% CI: 1.3–2.5, P=0.0004). The 1-year OS was 19 and 46%, respectively, for patients with a baseline CA19-9 above or below the median value. A fall of 20% in CA19-9 level from baseline was an independent prognostic factor for OS (HR 1.9; 95% CI: 1.1–3.4, P=0.019).British Journal of Cancer (2005) 93, 740–743. doi:10.1038/sj.bjc.6602760 www.bjcancer.com Published online 20 September 2005 [ABSTRACT FROM AUTHOR]

Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m(-2) twice daily) days 1-14 every 3 weeks and MMC (7 mg m(-2) IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40-77), and 23 patients (78%) were performance status 0-1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6-6.2). Median overall survival was 9.3 months (95% CI: 6.9-11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule. [ABSTRACT FROM AUTHOR]

The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50?mg?m-2, C 60?mg?m-2 and O 130?mg?m-2 i.v. 3 weekly; F 200?mg?m-2?day-1 i.v. and X 500?mg?m-2?b.i.d.-1 (escalated to 625?mg?m-2?b.i.d.-1 after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1%of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625?mg?m-2?b.i.d.-1 was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7%pts receiving F, 8.4%pts receiving X 500?mg?m-2?b.i.d.-1 and 14.7%pts receiving X 625?mg?m-2?b.i.d.-1. Combined complete and partial response rates were ECF 31%(95%CI 18.7-46.3), EOF 39%(95%CI 25.9-53.1), ECX 35%(95%CI 21.4-50.3), EOX 48%(95%CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7%of pts treated with X 625?mg?m-2?b.i.d.-1, which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.British Journal of Cancer (2005) 92, 1976-1983. doi:10.1038/sj.bjc.6602572 www.bjcancer.com [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether epirubicin, cisplatin and infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and leucovorin (FELV) in patients with previously untreated advanced biliary cancer in a prospective randomised study. Patients were randomly assigned to receive epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin (FELV). The primary end point was OS with secondary end points of objective response rate (ORR), failure-free survival (FFS), quality of life (QOL) and toxicity. In all, 54 patients were recruited with 27 randomly assigned to each arm. The median OS for ECF was 9.02?months (95%confidence interval (CI): 6.46-11.51) and FELV 12.03 months (95%CI: 9.3-14.7), P=0.2059. Objective response rates were similar for both arms: ECF 19.2%(95%CI: 6.55-39.3); FELV 15%(95%CI: 3.2-37.9), P=0.72. There was significantly increased grade 3/4 neutropenia with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was impressive for both regimens. This is the largest reported randomised study to date in this setting. ECF did not improve OS compared to FELV, but was associated with less acute toxicity. These data suggest that chemotherapy can prolong OS and achieve good symptomatic relief in advanced biliary cancer.British Journal of Cancer (2005) 92, 1650-1654. doi:10.1038/sj.bjc.6602576 www.bjcancer.com Published online 26 April 2005 [ABSTRACT FROM AUTHOR]

Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall survival and an irinotecan-specific toxicity composite end point (TCE) defined as the occurrence of grade 3 or 4 diarrhoea, neutropenia, febrile neutropenia, fever, infection or nausea and vomiting. Between 1997 and 2003, 339 eligible patients with advanced colorectal cancer (CRC) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered in a multicentre randomised trial. All patients commenced irinotecan at 350 mg m(-2) once every 3 weeks. There were no differences in proportions of patients developing TCE by age (<70 vs > or =70 : 37.8 vs 45.8%; P=0.218), PS (0-1 vs 2 : 39.3 vs 41.5%; P=0.793) or prior RT (RT vs no RT : 45.1 vs 38.5%; P=0.377). Males experienced more toxicity than females (44.3 vs 32.6%; P=0.031), but this was not significant after controlling for other co-variates (P=0.06). Patients aged > or =70 had similar objective responses (11.1 vs 9%; P=0.585) and survival (median 9.4 vs 9 months; log rank P=0.74) compared to younger patients. Elderly patients derive the same benefit without experiencing more toxicity with second-line irinotecan treatment for advanced CRC. Our data do not support the recommendation to reduce the starting dose for the elderly patients. [ABSTRACT FROM AUTHOR]