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Introduction: The diagnosis and quantification of chemotherapy-induced peripheral neuropathy (CIPN) remains a challenge. Conventional methods including quantitative sensory testing (QST), nerve conduction tests, and biopsy are unable to detect subclinical changes, and do not consistently correlate with severity of patients' symptoms and functional impairment. This study aims to determine the utility of the LDI (laser Doppler imager) FLARE technique in the diagnosis of CIPN and whether it correlates with symptom severity. Materials and Methods: We assessed 24 patients with established CIPN [12 due to platinum analogs (PA) and 12 to Taxanes (TX)] and 24 matched healthy controls (HC). All underwent neurophysiological examination including vibration perception threshold (VPT), sural nerve amplitude (SNAP) and conduction velocity (SNCV), LDIFLARE, and fasting biochemistry. The QLQ-CIPN20 questionnaire was used to assess symptom severity. Results: HC, combined chemotherapy (CG), PA, and TX groups were matched for age, sex, BMI, and blood pressure. The LDIFLARE was significantly reduced in CG compared to HC (P =< 0.0001), whereas SNAP (P = 0.058) and SNCV (P = 0.054) were not. The LDIFLARE correlated with the QLQ-CIPN20 symptom scores in all three categories namely, CG (P =< 0.0001), PA (P = 0.001) and TX (P = 0.027) whilst, VPT, SNAP, and SNCV did not. Conclusion: Our findings suggest that the LDIFLARE technique is more helpful in confirming the diagnosis of CIPN in patients with distal sensory symptoms than current commonly used methods. Moreover, this novel test fulfils the unmet need for a diagnostic test that relates to the severity of symptoms. This may be useful in quantifying early changes in small fibre function indicating early CIPN. [ABSTRACT FROM AUTHOR]

Lobular neoplasia is increasingly being detected, probably due to the widespread screening for breast malignancies. The understanding of lobular neoplasia is undergoing a paradigm shift, from being considered a predictor of recurrence to being considered a pre-invasive lesion, based on molecular studies suggesting a clonal link with invasive lobular cancer. The management of patients diagnosed to have lobular neoplasia is in evolution, with the increasing need for risk stratification and hence the necessity to identify this entity separately as either lobular carcinoma in-situ and atypical lobular hyperplasia. The indications for wide local excision for patients diagnosed to have lobular neoplasia on biopsy are being defined. The evidence for preventive strategies like hormonal treatment with Tamoxifen or aromatase inhibitors for high risk patients is increasing, with the results from prospective interventional trials. The role of screening magnetic resonance imaging for surveillance of high risk patients with lobular neoplasia is under evaluation. [ABSTRACT FROM AUTHOR]

Background: Ewing's sarcoma of extra-skeletal origin is uncommon and those of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods: A retrospective review of the clinical features, treatment and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993 - December 2007 is reported. Results: Seven adult patients with primary renal Ewing's sarcoma were identified. All four patients with non metastatic disease had radical nephrectomy, and received adjuvant chemotherapy +/- radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease free survival in patients with non metastatic disease after combined modality treatment was 30.3 months. Conclusion : Primary adult renal Ewing's sarcoma is an aggressive tumour with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the prostate-specific antigen (PSA) response rate and duration of PSA response to dexamethasone in patients with castration-refractory prostate cancer (CRPC), as corticosteroids are frequently used as second-line hormonal treatment of CRPC and there is little published evidence concerning the efficacy of low-dose dexamethasone in this setting. PATIENTS AND METHODS In all, 102 patients with progressive CRPC received oral dexamethasone (0.5 mg daily) between January 2003 and October 2006. The median pretreatment PSA level was 83 ng/mL. The main endpoint was the PSA response rate according to the PSA Working Group criteria. RESULTS In all, 50 patients (49%) had a confirmed PSA response. The median (range) time to PSA progression for the entire cohort was 7.4 (1–28) months. In responders, the median duration of the PSA response was 11.6 (1–24) months. CONCLUSION Low-dose dexamethasone has significant activity in CRPC. Subject to validation with more clinically meaningful endpoints, dexamethasone could become the corticosteroid of choice in the management of CRPC, and its potential for use in combination with novel agents should be explored. [ABSTRACT FROM AUTHOR]

OBJECTIVE To report the results of a prospective study of active surveillance of untreated prostate cancer, with a focus on baseline predictors of prostate-specific antigen (PSA) velocity, as PSA velocity before treatment is an important predictor of prostate cancer mortality, and patients on active surveillance are monitored for several years to estimate the PSA velocity and thus select patients for radical treatment. PATIENTS AND METHODS A prospective study of active surveillance for localized prostate cancer opened at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a, N0/Nx, M0/Mx adenocarcinoma of the prostate with a serum PSA level of <15 ng/mL, a Gleason score of ≤7 with primary grade ≤3, and less than half the biopsy cores positive. The PSA velocity before treatment was analysed in relation to baseline clinical characteristics. RESULTS In all, 237 patients on surveillance were followed for a median of 24 months (median age 67 years; median initial PSA level 6.5 ng/mL; median pretreatment PSA velocity 0.44 ng/mL per year). On multivariate analysis, PSA density (i.e. serum PSA level/prostate volume) was the only significant determinant of PSA velocity ( P < 0.001). Patients with a PSA density above or below the median (0.185 ng/mL/mL) had a median (interquartile range) PSA velocity of 0.92 (0.34–1.77) ng/mL per year and 0.35 (− 0.06, 0.80) ng/mL per year, respectively. CONCLUSIONS PSA density, which is readily available at the time of diagnosis, is an independent determinant of PSA velocity in untreated, localized prostate cancer. If this is confirmed, PSA density could be used to inform the often difficult choice between active surveillance and immediate radical treatment. [ABSTRACT FROM AUTHOR]

Aims: To compare voice quality as defined by formant analysis using a sustained vowel in patients who have undergone a partial glossectomy with a group of normal subjects. Methods & Procedures: The design consisted of a single centre, cross-sectional cohort study. The setting was an Adult Tertiary Referral Unit. A total of 26 patients (19 males) who underwent partial glossectomy and 31 normal volunteers (18 males) participated in the study. Group comparisons using the first three formant frequencies (F1, F2 and F3) using linear predictive coding (Laryngograph Ltd, London, UK) were performed. The existence of any significant difference of F1, F2 and F3 between the two groups using the sustained vowel /i/ and the effects of other factors, namely age, first presentation versus recurrence, site (oral cavity, oropharynx), subsite (anterior two-thirds of the tongue, tongue base), stage, radiation, complication, and neck dissection, were analysed. Outcomes & Results: Formant frequencies F1, F2 and F3 were normally distributed. F1 and F2 were significantly different in normal males versus females. F1, F2 and F3 were not different statistically between male and female glossectomees. Comparison of only women showed significant differences between normal subjects and patients in F2 and F3, but none in F1. This was the opposite in men where F1 was significantly different. Age, tumour presentation, site, subsite, radiation and neck dissection showed no significant difference. Postoperative complications significantly affected the F1 formant frequency. Conclusions: The study found that the formant values in patients following a partial glossectomy were altered significantly as compared with the normal control subjects. Only gender and complications and not the age, site, subsite, radiation and neck dissection were seen to influence the formant scores. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the utility of lactate dehydrogenase (LDH), a tumour marker that is frequently elevated at diagnosis and relapse of testicular germ cell tumours (TGCTs), in the follow-up of TGCTs for detecting tumour relapse, as it has role as a prognostic factor but its role in follow-up is less certain. PATIENTS AND METHODS We retrospectively reviewed 499 patients with TGCT who were followed from 1 January 2004 to 31 December 2005, with no clinical evidence of disease after a complete response to treatment or on surveillance for stage I disease. RESULTS Of patients attending for follow-up or surveillance, in 26 of 1777 (1.4%) ‘patient-visits’ there was a high LDH level related to disease, and in 137 of 1777 (7.7%) such visits there was a high LDH from unrelated causes. Of the 499 patients who were followed, 15 relapsed; the LDH level was high in six of 15 who relapsed, with LDH being one of the first elevated markers in four and the only elevated marker in one (seminoma). Of the 449 patients, 41 (9.1%) had a persistent false-positive increase in LDH. The sensitivity of LDH was 40%, the specificity 90.5% and the positive predictive value 12.8% to detect relapse of disease during the follow-up of TGCTs. When the series of 116 relapsed patients from 1992 to 2005 was analysed, an increase in LDH facilitated the detection of relapse in 2% of non-seminomatous GCTs and 11% of seminomas, independent of other markers. CONCLUSION LDH has limited sensitivity, specificity and positive predictive value for detecting relapse of TGCT and false-positive increases are common. An elevated LDH level contributed to the detection in six of 15 relapses, suggesting that its value in the follow-up of TGCT might be useful if interpreted cautiously. High LDH levels during the follow-up might require repeat serial LDH estimates to confirm the elevation, and imaging to detect a relapse. [ABSTRACT FROM AUTHOR]