inflammation

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Ketamine: only for fools and horses

February 17, 2014/3 Comments/by Dan Wood

There are many terrifying anecdotes relating to the use of ketamine and the damage that sustained daily use may cause to the urinary tract. These include those reported in the medical literature and through the wider media. Reports of ketamine-related deaths, memory loss, hepatobiliary damage, ureteric obstruction with renal failure and profound bladder pain. Use is recorded in teenagers with the ability for a child to demonstrate symptoms to their peers becoming a badge of honour. At UCLH we are working closely with colleagues to provide improving care for this new disease. We have links with the Club Drug clinic in London and Lifeline, another drug support agency. We aim to help patients come off ketamine and re-assess their symptoms once that is true – a few patients have needed major surgery but many have recovered well without.

The drug is now the most widely used drug of abuse in China – its use appears to be growing elsewhere. In the UK figures from the Home Office in 2013 suggested that 120,000 16–59 year olds had used ketamine over the preceding 12 months. Experts have suggested that between 20 and 30% of daily users will develop urinary symptoms. This was confirmed in a recent survey of ketamine users where 27% reported urinary symptoms and only half improved with cessation.

Many myths exist about how ketamine can be safe if taken with lots of water or that it is not addictive – neither of which are true. With appropriate questioning we can and do recognize the link between ketamine and damage to the urinary tract. As urologists we are less well informed about the other risks such as the psychological or hepatobiliary damage that are also seen. Support for rehabilitation and cessation of ketamine lies in the hands of a few interested groups and is certainly not widespread. However, there is universal agreement that cessation is a vital component of treatment – patients will often see a substantial improvement in symptoms. Many users seeking help for urological symptoms struggle to find informed support to help come off the drug. It has been suggested that there is little money to support agencies in helping people to stop ketamine use – this may be due to a lack of criminal activity linked to ketamine. Whilst the damage to an individual may be significant – the impact on society is perceived as small and this appears to reflect the money available to tackle it.

Last week in the UK, as the media reported the death of an 18 year old girl from ketamine, the government announced it had accepted the recommendation of the Advisory Council on Misuse of Drugs and that it was upgrading ketamine from class C to a class B drug.

Reclassification from Class C to B will put ketamine alongside codeine, cannabis, amphetamine and mephedrone. This increases the prison term for possession from two to five years. It remains to be seen whether this will have any direct effect. If it sends a clear message that taking recreational ketamine does you harm or it facilitates an improved environment and support for ketamine cessation then that may benefit some. To the uninitiated the potential risks may be that reclassification could push up cost and that adulterants may be further introduced. This could add to the unpredictability of an effect that even now requires further clarification.

The fact that the issues surrounding ketamine are being discussed is important – it will help users, potential users and healthcare professionals to recognize the symptoms and the risks. Much wider and more detailed education is needed to try and prevent damage to more users.

Mr Dan Wood
Consultant in Adolescent and Reconstructive Urology
University College London Hospitals
Honorary Consultant Urologist, Great Ormond Street Hospital
Honorary Senior Lecturer University College London

Twitter @drdanwood

Article of the week: Rethinking inflammation in PCa

October 23, 2013/by admin Z.9

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate-specific antigen (PSA) concentration in the Finnish prostate cancer screening trial

Tytti H. Yli-Hemminki*^†, Marita Laurila*, Anssi Auvinen^‡, Liisa Määttänen^§, Heini Huhtala^‡, Teuvo L.J. Tammela^¶ and Paula M. Kujala*

*Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, ^†Department of Pathology, Seinäjoki Central Hospital, Seinäjoki, ^‡School of Health Sciences, University of Tampere, Tampere, ^§Finnish Cancer Registry, Helsinki, and ^¶Department of Urology, Tampere University Hospital and University of Tampere, Tampere, Finland

T. H. Y.-H. and M. L. contributed equally to this study.

Read the full article

OBJECTIVE

• To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate-specific antigen (PSA) concentrations and benign initial biopsy.

MATERIALS AND METHODS

• Study subjects were men aged 54–67 years with an elevated PSA (≥4 ng/mL or 3–4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996.

• A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation.

• Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry.

• The median length of follow-up was 10.5 years.

• Cox regression analysis was used to assess PCa risk after the initial benign biopsy.

RESULTS

• Histological inflammation was found in 66% of the biopsies.

• Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35–1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46–1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42–1.07; P = 0.092).

CONCLUSIONS

• Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance.

• Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.

Read Previous Articles of the Week

Editorial: Does inflammation reduce the risk of prostate cancer?

October 23, 2013/1 Comment/by Roger Kirby

Chronic inflammation is thought to play an aetiological role in tumorigenesis in several cancers including bladder, oesophagus and liver [1]. Molecular studies show that it plays a critical role in several stages of the carcinogenic process including tumour initiation, promotion, metastases and response to therapy. However the role in prostate cancer is less clear and to date, clinical studies are inconclusive.

The article in this issue of BJUI by Yli-Hemminki et al. [2] appears to show an inverse association with histological inflammation and the risk of prostate cancer. Using data from the Finnish subgroup of the European Randomised Study of Prostate Cancer Screening (ERSPC) study they examined 293 patients with previous negative biopsies over a 10.5-year period and reported an 18% risk of prostate cancer in men with inflammation on initial biopsy (34 of 101 men) as opposed to 27% in those without inflammation (51 of 192 men). Perhaps somewhat surprisingly, histological inflammation did not appear to be significantly associated with PSA concentration, although it did appear that the free/total PSA ratio was higher in men with inflammation.

One potential confounding factor is that inflammation may also play a role in the pathogenesis of BPH. A large scale study showed that the odds ratio for BPH was 8.0 with a history of prostatitis [3]. Furthermore, the Medical Therapy of Prostatic Symptoms (MTOPS) study showed that men with inflammation had a significantly higher risk of BPH progression and acute urinary retention. These factors may impact on PSA levels and the chance of a subsequent prostate biopsy. However, the authors report that the inverse association of prostate cancer and inflammation did not alter when corrected for prostate volume, PSA level and age.

Significantly, those patients who screened positive at first biopsy were already excluded as were those with a suspicion of prostate cancer, such as a small atypical focus. Despite this, the study group probably represents high-risk patients, as they had all previously met the criteria for the first round of biopsies. This is borne out by the fact that the risk of prostate cancer was significantly increased when the men with inflammation on biopsy were compared with the initially screened negative men (hazard ratio 4.3). Unfortunately, we do not know what the rate of inflammation was in the control arm as they were screened negative and hence no biopsies were taken.

The significance of PSA level or prostatic intraepithelial neoplasia was not specifically investigated, although the reported rates were 32.1% and 7.5% respectively. Overall the incidence of inflammation was reported as 65%, but this included both acute and chronic inflammation. A smaller number of patients were given grade 2/3 chronic inflammation (80 and 20 patients, respectively) and only 14 patients had grade 2/3 acute, indicating most had milder degrees of inflammation. Whether this is a representative sample is not entirely clear. As the authors comment, published rates of histological inflammation do vary significantly from 8 to 99% and this does appear to vary according to detection method.

Several case-control studies and a meta-analysis [4] have shown that there is a significant increase in the relative risk of prostate cancer in men with prostatitis; however, these epidemiological studies all suffer from selection bias, in that men with clinical symptoms are more likely present and to be investigated and followed up by a Urologist. This study [2] only examines the role of histological inflammation and, at least partially, removes the selection bias associated with clinical symptoms, although it could still be argued that men with clinical prostatitis may be more likely to present for screening. This study represents a highly selected group of patients that are high risk for prostate cancer and no firm conclusions can be drawn on the general population. As inflammation is so common in prostate specimens, further high-quality large-scale studies are needed with similar long-term follow-up.

Miles A. Goldstraw and Roger S. Kirby
The Prostate Centre, London, UK