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H Kynaston

Publications and source records attributed to H Kynaston.

13 recordsLinked to original sources
PubMed2004

Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials.

OBJECTIVE: To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical mitomycin C and bacillus Calmette-Guérin (BCG) for tumour recurrence, disease progression and overall survival in patients with medium- to high-risk Ta and T1 bladder cancer. METHODS: The major medical databases were searched comprehensively up to June 2003, and relevant journals hand-searched for randomized controlled trials, in any language, that compared intravesical mitomycin C with BCG in medium- to high-risk patients with Ta or T1 bladder cancer. RESULTS: Twenty-five articles were identified but only seven were considered eligible for the analysis. This represented 1901 evaluable patients in all, 820 randomized to mitomycin C and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin and 834 in the BCG arm. There was no significant difference between mitomycin C and BCG for tumour recurrence in the six trials, with a weighted mean log hazard ratio, LHR, (variance) of -0.022 (0.005). However, there was significant heterogeneity between trials (P = 0.001). A subgroup analysis of three trials that included only high-risk Ta and T1 patients indicated no heterogeneity (P = 0.25) and a LHR for recurrence of -0.371 (0.012). With mitomycin C used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, was highly significant (P < 0.001). The seventh trial (in abstract form only) used BCG in low doses for two arms of the trial (27 mg and 13.5 mg) compared with a standard dose of mitomycin C (30 mg), and reported a significantly lower recurrence rate with BCG (27 mg) than for mitomycin C (P = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing 681 patients (338 randomized to BCG and 343 to mitomycin C). There was no significant difference between mitomycin C and BCG for disease progression, with a LHR of 0.044 (0.04) (P = 0.16), or survival, at -0.112 (0.03) (P = 0.50). Adverse events were slightly more frequent with BCG. Local toxicity (dysuria, cystitis, frequency and haematuria) were associated with both mitomycin C (30%) and BCG (44%). Systemic toxicity, e.g. chills, fever and malaise, occurred with both agents (12% and 19%, respectively) although skin rash was more common with mitomycin C. CONCLUSION: Tumour recurrence was significantly lower with intravesical BCG than with mitomycin C only in those patients at high risk of tumour recurrence. However, there was no difference in disease progression or survival, and the decision to use either agent might be based on adverse events and cost.

Adjuvants, Immunologic↗
PubMed2003

Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer.

BACKGROUND: Tumour recurrence following transurethral resection (TUR) for Ta and T1 bladder cancer is a major clinical problem. Intravesical administration of mitomycin C (MMC) or bacillus Calmette-Guerin (BCG) has proven prophylactic activity but both are associated with local and systemic side-effects. A systematic review was carried out to compare the efficacy of these two agents. OBJECTIVES: To undertake a systematic review and meta-analysis comparing intravesical mitomycin C and Bacillus Calmette-Guerin in terms of tumour recurrence, disease progression and overall survival in Ta and T1 bladder cancer. Treatment-related toxicities would also be evaluated. SEARCH STRATEGY: A comprehensive search of MEDLINE, EMBASE, Healthstar, Cochrane Controlled Trials Register, Cancerlit, and DARE was performed, and hand searching of relevant journals undertaken. SELECTION CRITERIA: Trials in any language were included in the meta-analysis if they were properly randomised, included medium to high risk patients with Ta or T1 bladder cancer and compared intravesical MMC versus BCG. DATA COLLECTION AND ANALYSIS: Trial eligibility, methodological quality and data extraction were assessed independently by two reviewers. Time to event analysis was evaluated using log hazard ratios, with a sensitivity analysis for subgroups according to patient's risk of recurrence. MAIN RESULTS: Twenty-five articles were identified but only seven were considered eligible. This represented 1901 evaluable patients in total, 820 randomised to MMC and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin arm and 834 in the BCG arm. The weighted mean log hazard ratio (variance) for tumour recurrence for the six trials was - 0.022 (0.005). This indicated no significant difference between MMC and BCG (p = 0.76). However, the meta-analysis indicated evidence of significant heterogeneity between trials (p = 0.001). A subgroup analysis of three trials that included only high risk Ta and T1 patients indicated no heterogeneity (p = 0.25) and a log hazard ratio (variance) for recurrence of -0.371 ( 0.012). With MMC used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, is highly significant (p = 0.0008). The seventh trial, in abstract form only, used BCG in low doses for two arms of the trial (27 mg and 13.5mg) compared to a standard dose of mitomycin C (30mg), and reported a significantly reduced recurrent rate with BCG (27mg) compared to mitomycin C (p = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing a total of 681 patients; 338 randomised to BCG and 343 to MMC. There was no significant difference between MMC and BCG for disease progression (log hazard ratio + variance: 0.044 + 0.04, p = 0.16) or survival (-0.112 + 0.03, p = 0.50). Local toxicities (dysuria, cystitis, frequency, and haematuria) were associated with both MMC (30%) and BCG (44%). Systemic toxicities, such as chills, fever and malaise, were observed with both MMC and BCG (12% and 19%, respectively) although skin rash was more common with MMC. REVIEWER'S CONCLUSIONS: The data from the present meta-analysis indicate that tumour recurrence was significantly reduced with intravesical BCG compared to MMC only in the subgroup of patients at high risk of tumour recurrence. However, there was no difference in terms of disease progression or survival, and the decision to use either agent might be based on adverse events and cost.

Administration, Intravesical↗
PubMed2002

The prevalence and predictors of psychological distress in patients with early localized prostate cancer.

OBJECTIVE: To determine the level of psychopathology, traumatic distress and quality of life in men with newly diagnosed clinically localized prostate cancer, the effect on these of a consultation in a combined-specialist early-prostate clinic, and predictors of psychopathology. PATIENTS AND METHODS: Eighty-eight patients were recruited from the combined clinic; they completed a battery of questionnaires including the Hospital Anxiety and Depression Scale (HADS), the revised Impact of Event Scale (IES) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, before their first appointment. Two weeks later they completed the HADS, IES and a patient-satisfaction survey. RESULTS: The overall level of psychopathology varied among the questionnaires used, from 0% on the HADS depression scale, 8% on the HADS anxiety scale and 14% on the IES. Anxiety and traumatic stress symptoms were commoner than depressive symptoms. The quality-of-life scores showed a relatively good level of functioning. Pre-morbid factors and disease status did not predict psychological distress. Younger age was mildly predictive of poorer psychological functioning. Anxiety symptoms reduced slightly after a joint clinic appointment, whereas depressive symptoms showed a slight increase. CONCLUSION: This study suggests that men with early localized prostate cancer have low levels of psychopathology overall. However, some men experience distressing psychological symptoms and it is important that future research is conducted to help develop clear guidelines on the optimal methods of detecting and managing men with prostate cancer who have mental health difficulties.

Aged↗
PubMed2001

A systematic review of intravesical bacillus Calmette-Guérin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer.

OBJECTIVE: To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer. PATIENTS AND METHODS: An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer. RESULTS: The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was -0.83 (95% confidence interval -0.57 to -1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21-0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. CONCLUSION: TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.

Administration, Intravesical↗
PubMed2000

Intravesical Bacillus Calmette-Guerin in Ta and T1 Bladder Cancer.

BACKGROUND: Intravesical therapy with Bacillus Calmette-Guerin (BCG) aims to reduce the incidence of tumour recurrence following transurethral resection (TUR) for patients with superficial bladder cancer. OBJECTIVES: The objective of this review was to compare the incidence of tumour recurrence after the standard therapy of transurethral resection versus transurethral resection plus intravesical Bacillus Calmette-Guerin. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (March 2000), Medline (February, 2000), EMBASE (February, 2000), Cancerlit (February, 2000), Healthstar (February, 2000), Database of Abstracts of Reviews of Effectiveness (February, 2000) and the Bath Information Data Service. The Proceedings of the American Society Clinical Oncology was hand searched (1996 - 1999). SELECTION CRITERIA: Randomised or quasi-randomised trials of transurethral resection alone versus transurethral resection plus intravesical Bacillus Calmette-Guerin. Patients with Ta and T1 bladder cancer of medium or high risk of tumour recurrence, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Four reviewers assessed trial quality and two abstracted the data independently. The Peto odds ratios and log hazard ratios were determined to compare the number of patients with disease recurrence at 12 months and the rate of recurrence, respectively. MAIN RESULTS: Six randomised trials were included involving 585 eligible patients. There were significantly fewer patients with disease recurrence at 12 months in the BCG plus TUR group compared to those that received TUR alone (odds ratio 0.30, CI 0.21, 0.43). The overall log hazard ratio for recurrence (-0.83, variance 0.02) indicated a significant benefit of BCG treatment in reducing tumour recurrence. Toxicities associated with BCG consisted mainly of cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. REVIEWER'S CONCLUSIONS: In patients with medium/high risk Ta or T1 bladder cancer, immunotherapy with intravesical BCG following TUR appears to provide a significant advantage over TUR alone in delaying tumour recurrence.

Adjuvants, Immunologic↗
PubMed1997

Effects of octreotide on liver regeneration and tumour growth in the regenerating liver.

The ability of the liver to regenerate following resection is remarkable. However, there is evidence to suggest that tumour growth within the regenerating liver is significantly increased. As octreotide (a synthetic analogue of somatostatin) inhibits the growth and development of hepatic tumour in rats, we have investigated its effects on liver regeneration, liver blood flow, hepatic reticuloendothelial system activity and tumour growth in the rat following partial hepatectomy (PH). Octreotide significantly inhibited liver regeneration in the rat 1 and 2 weeks following PH when compared with controls (regeneration index: 1.0 and 1.14 cf. 1.14 and 1.4, respectively). There was no significant difference in hepatic arterial or portal venous blood flow following PH in control or octreotide-treated rats. However, portal pressure was significantly reduced in octreotide-treated rats. Hepatic reticuloendothelial system activity was significantly increased in octreotide-treated rats compared with control animals 1 and 2 weeks after hepatectomy (uptake of radiolabelled technetium-99m albumin colloid: 2.2 and 3.9 cf. 1.6 and 1.9). The growth of both HSN (fibrosarcoma) and K12-Tr (colonic adenocarcinoma) cells in the regenerating liver was significantly decreased by octreotide treatment compared with controls (median percentage hepatic replacement: HSN control 71.3%, Octreotide 8.4%, K12-Tr Control 38.3%, Octreotide 4.5%). The results of the present study demonstrate that octreotide inhibits both liver regeneration and tumour growth following PH, possibly via a similar mechanism.

Animals↗
PubMed1995

Octreotide inhibits the growth and development of three types of experimental liver metastases.

A study was performed to assess the effects of octreotide on the growth and development of liver metastases in rats. Tumour was induced by intraportal injection of three tumorigenic cell lines (the fibrosarcoma HSN and colonic adenocarcinomas K12/Tr and WB2054M) in syngeneic rats. Octreotide treatment (2 micrograms subcutaneously for 3 or 4 weeks) was started 18 h and 1 week after tumour induction; a delay in treatment of 1 week allowed micrometastases to develop. Treatment with octreotide significantly (P < 0.001) reduced the median hepatic replacement of liver by tumour compared with that of control rats given saline (controls: HSN 76.4 per cent, K12/Tr 17.5 per cent, WB2054M 43.9 per cent; octreotide treatment delayed 18 h: HSN 2.7 per cent, K12/Tr 0.6 per cent, WB2054M 1.3 per cent; octreotide treatment delayed 1 week: HSN 9.3 per cent, K12/Tr 2.5 per cent, WB2054M 2.3 per cent). These results clearly indicate that octreotide significantly inhibits the growth and development of experimental liver metastases. Further studies are required both to delineate the mechanism of action and to investigate these effects in a clinical setting.

Animals↗
PubMed1995

Effect of octreotide infusion on hepatic and tumour blood flow in two experimental models of liver metastases.

OBJECTIVE: To investigate the effects of octreotide infusion on hepatic and tumour blood flow in rats with experimentally induced liver tumours. DESIGN: Blood flow was determined in tumour-bearing rats using a dual reference microsphere technique before and after intravenous infusion of octreotide. METHODS: Tumours were induced in syngeneic rats by intraportal injection of K12-Tr and WB2054-M adenocarcinoma cells. Hepatic arterial and portal venous inflow, tumour blood flow and systemic arterial pressure were determined before and after octreotide infusion (0.05 microgram/min). RESULTS: In rats with K12-Tr tumours there was no change in tumour blood flow, hepatic arterial flow or portal venous inflow after octreotide infusion. In contrast, in rats with WB2054-M tumours, octreotide infusion resulted in a significant reduction in the blood flow to the hepatic tumour (from 0.37 to 0.135 ml/min/g) but had no effect on hepatic artery or portal venous inflow. CONCLUSION: The reduction in blood flow to tumours derived from WB2054-M cells could, at least in part, explain the inhibitory effect of octreotide on the growth and development of these tumours. However, octreotide had no effect on blood flow to tumours derived from K12-Tr cells, suggesting that the analogue must inhibit tumour growth by other mechanisms.

Adenocarcinoma↗
PubMed1995

Octreotide, the reticuloendothelial system, and experimental liver tumour.

The inhibitory effect of octreotide on the growth of liver tumour is probably mediated (at least in part) by stimulation of the hepatic reticuloendothelial system (RES) activity. This study therefore investigated the effect of octreotide on the hepatic and splenic RES (assessed by the uptake of technetium 99m labelled albumin colloid, 99mTc-AC) in normal and tumour bearing rats and in animals treated with gadolinium chloride. The effects of gadolinium chloride and octreotide alone or in combination on the growth of liver tumour were also studied. Octreotide significantly stimulates both hepatic and splenic uptake of 99mTc-AC in normal rats and tumour bearing rats. In controls, the uptake of 99mTc-AC was significantly reduced by gadolinium chloride and was not changed by octreotide. RES blockade with gadolinium chloride significantly increased (p < 0.001) tumour growth compared with controls (hepatic replacement 42%; 95% confidence intervals (CI), 27.6 to 56.4 v 16.7%, 95% CI, 11.1 to 21.3%) whereas octreotide significantly inhibited (p < 0.001) the percentage hepatic replacement by tumour (0.7%; 95% CI, 0 to 2.3 v 16.7%; 95% CI, 11.1 to 21.3). This study highlights the importance of the RES in the development of liver tumour. Furthermore, octreotide inhibited the growth of liver tumour in rats with RES blockade, albeit to a lesser degree than in normal animals. These findings suggest that octreotide inhibits the growth of hepatic tumour by mechanisms other than stimulation of RES activity.

Animals↗
PubMed1994

A prospective randomized trial comparing a modified needle suspension procedure with the vagina/obturator shelf procedure for genuine stress incontinence.

OBJECTIVE: To compare two procedures for the treatment of genuine stress incontinence in patients selected randomly. PATIENTS AND METHODS: Fifty patients with proven genuine stress incontinence were randomized prospectively over a 3 year period to be treated either by a modified needle suspension (MNS) (n = 26) or by a vagina/obturator shelf (VOS) (n = 24) procedure. RESULTS: In patients who had not undergone previous surgery for incontinence, the VOS procedure was superior with 12 of 14 patients achieving continence compared with eight of 15 patients in the MNS group (P < 0.05). In women who had undergone previous surgery seven of 11 were continent following MNS compared with five of 10 after a VOS procedure. Both techniques had a much lower continence rate when compared with a classical colposuspension operation which was reported in a previous series. CONCLUSION: As a primary procedure VOS was more successful than MNS. In patients who had undergone previous surgery for incontinence neither procedure gave acceptable results.

Female↗
PubMed1993

Reticuloendothelial stimulation: levamisole compared.

PURPOSE: Levamisole in combination with 5-fluorouracil is an effective adjuvant for the treatment of resected Dukes stage C colon cancer. Since the mechanism of action of levamisole is not known, we have investigated its effects on hepatic and splenic reticuloendothelial system (RES) activity in the rat and compared the effect of levamisole with other known RES stimulators. METHODS: The hepatic and splenic uptake of an intravenous dose of technetium-99m-sulfur colloid has been used to measure RES activity in rats treated with levamisole, glucan, zymosan, chlormethiazole, octreotide, and saline. RESULTS: Levamisole significantly increased the hepatic uptake of technetium-99m-sulfur colloid and is comparable in its effect to the other RES stimulators. In contrast, levamisole has no effect on splenic RES activity. CONCLUSION: RES function is considered to be a potentially important factor in the development of liver metastases, and the stimulatory effect of levamisole on the hepatic RES may partly explain its efficacy as an adjuvant treatment in colon cancer.

Animals↗
PubMed1992

Amyloid tumour of the urethra presenting as non-specific urethritis.

Amyloid tumour involving the urethra is a well recognised but rare occurrence. Chronic inflammation secondary to gonococcal urethritis is thought to be a possible predisposing factor. We report the case of a young man who presented with non-gonococcal urethritis and haematuria and was subsequently found to have primary amyloid of the urethra.

Adult↗