Most of our social scientists are not institution based ... they are there for hire -- Research consultancies and social science capacity for health research in East Africa There is a serious shortage of senior African social scientists to lead health-related research in Africa . This is despite the existence of many African social science graduates , and decades of Northern funded research programmes intended to develop local capacity . To investigate the barriers to developing health social science research capacity in East Africa , 29 in-depth interviews , informal conversations and a group discussion were conducted with professionals in this field . Introduction There is a serious shortage of senior African social scientists to lead or manage health-related research in Africa -LRB- World Bank , 2000 -RRB- . This is despite the graduation of many African social scientists , and decades of Northern funded research programmes intended to develop local capacity -LRB- Nchinda , 2002 ; Simon , 2000 -RRB- . Whilst weak research capacity probably affects all areas of health , the HIV epidemic ` offers a supreme test of how effectively African universities can respond to emerging challenges ... ' -LRB- Zeleza , 2003 , p. 84 -RRB- . Yet the shortage of senior social scientists is particularly apparent in sexual health . For instance , large-scale HIV/AIDS research programmes in both Tanzania and Uganda have been unable to recruit local social scientists to senior posts on international salaries , despite having trained local junior social scientists for over 10 years . Furthermore , international debates on social dimensions of sexual health , such as the hypothesis of permissive African sexuality -LRB- Caldwell , J , Caldwell , P , & Quiggin , 1989 -RRB- , are dominated by Northern academics , despite their sensitivity . Health-related social science research capacity is the ability to investigate and define the social dimensions of health problems , set objectives , identify solutions and build sustainable institutions -LRB- cf. Sitthi-amorn & Somrongthong , 2000 -RRB- . Limited capacity is problematic at several levels . Most obviously , it requires non-local researchers generally unfamiliar with local life , reliant on interpreters , and prone to cultural misunderstandings with local fieldworkers . Service providers and policy makers have to base decisions on more superficial analyses , but ex-patriate-initiated research is less likely to have such practical application anyway -LRB- Costello & Zumla , 2000 -RRB- . At the broadest level , limited social science capacity restricts intellectual sovereignty -LRB- Zeleza , 2003 -RRB- , undermining political autonomy -LRB- RAWOO , 2002 ; Sitthi-amorn & Somrongthong , 2000 -RRB- . The main explanations for limited research capacity have been identified in the literature as : inadequate resources for education at every level -LRB- Nchinda , 2002 ; Sall , 2003 ; Sitthi-amorn & Somrongthong , 2000 -RRB- ; the drain of expertise to the North -LRB- Pang , Lansang , & Haines , 2002 ; Ramsay , 2002 ; Sall , 2003 ; Zeleza , 2003 -RRB- ; dependence on Northern research funding -LRB- Jentsch & Pilley , 2003 ; Lansang & Dennis , 2004 -RRB- ; inequitable access to the literature -LRB- Lansang & Dennis , 2004 -RRB- ; unbalanced North -- South research collaborations -LRB- Costello & Zumla , 2000 ; Jentsch & Pilley , 2003 -RRB- and poor support from government -LRB- Nchinda , 2002 ; Sall , 2003 ; Sitthi-amorn & Somrongthong , 2000 -RRB- . Some see the perpetuation of inadequate research capacity as replicating the imbalance in global trade relationships -LRB- Zeleza , 2003 -RRB- and essentially semi-colonial -LRB- e.g. , Costello & Zumla , 2000 -RRB- . Others assume the good intentions of funders and research partners , but identify the perverse consequences of North -- South collaborations -LRB- Edejer , 1999 -RRB- , such as poaching senior researchers from local institutions . Either way , limited research capacity in Africa should be an ethical issue for Northern researchers working there . Whilst the main causes of weak research capacity are clearly macro-economic , the processes of conducting research might contribute to the problem and may be more readily modified -LRB- Green , 2003 -RRB- . Some reports have suggested that research consultancies , whilst augmenting meagre incomes , might marginalise teaching and research and undermine social science scholarship -LRB- Kwesiga , Mbago , & Chimanikire , 2000 ; Menken , Blanc , & Lloyd , 2002 ; Mkandawire , 1998 ; Sall , 2003 -RRB- . Being highly prescribed , consultancies have also been said to exacerbate the way African social science research is narrowly policy-bound -LRB- Allen , 1986 ; Sall , 2003 -RRB- , and increase Northern dominance of the research agenda -LRB- Mkandawire , 1998 -RRB- . ` ... consultants do not frequently choose to contradict the donor 's agenda , ... this would decrease their chances of ... consultancies in the future . ' -LRB- Rossi , 2004 , p. 27 -RRB- . Consultancies have been described as particularly problematic in East Africa -LRB- Sall , 2003 -RRB- , the University of Nairobi being called a ` consultancy university ' -LRB- Allen , 1986 , p. 25 -RRB- . There have been many attempts to strengthen research capacity in developing countries , leading sponsors being the WHO and other UN agencies -LRB- e.g. , the Special Programme for Research and Training in Tropical Diseases -LRB- TDR -RRB- ; UNDP/World Bank/WHO , 2003 -RRB- , national development agencies -LRB- e.g. , Swiss , Canadian and Japanese -RRB- , foundations such as Rockefeller and NGOs such as the Population Council . However , there is little evidence about the most effective approach -LRB- Simon , 2000 -RRB- , and debates continue over , for instance , investing in individuals or institutions -LRB- Costello & Zumla , 2000 ; Nchinda , 2002 -RRB- , whether post-graduate training in the North exacerbates the brain drain -LRB- Nchinda , 2002 -RRB- , and Southern control of research budgets -LRB- Lansang & Dennis , 2004 ; Nchinda , 2002 -RRB- . The role of consultancies , however , has received scant attention and almost exclusively in the grey literature . In order to investigate the poor capacity for health-related social science research in East Africa , the processes perpetuating it and possible ways to improve it , a small-scale exploratory study was conducted in Tanzania , Kenya and Uganda . The general findings have been reported elsewhere -LRB- Wight , 2005 -RRB- . This short report focuses on the individualised nature of research activity and the role of individual research consultancies in shaping research capacity . Methods In 2003 and 2004 , I conducted in-depth interviews with 29 leading professionals conducting , commissioning or supporting health-related social science research in East Africa -LRB- Table 1 -RRB- . The findings are biased towards Uganda , 18 interviewees being Ugandan , four Kenyan , three British , two North American , one Tanzanian and one Nigerian . This was primarily a snowball sample including seven senior social scientists from Makerere , the oldest university in East Africa with by far the largest research function in Uganda , and others from the London School of Hygiene and Tropical Medicine -LRB- three -RRB- , the Universities of Nairobi -LRB- two -RRB- and Dar es Salaam -LRB- one -RRB- and from the leading independent research centres and research-supporting NGOs in Uganda and Kenya . None of the new universities were represented . To protect respondents ' anonymity small institutions are not named . The interview schedule covered leadership of local social science research , training and career paths , ways of strengthening research capacity and barriers to this . The full schedule is available -LRB- as Appendix A -RRB- . Informal conversations were held with five senior and one junior researcher from the University of Dar es Salaam and National Institute for Medical Research , Tanzania , and nine junior researchers from Makerere and the MRC Programme on AIDS in Uganda . A group discussion was held with four of the Ugandans -LRB- three men , one woman -RRB- , following the same schedule used for the in-depth interviews . The interviews were summarised according to analytical themes . There was considerable concordance in accounts , which were not patterned by gender . Divergent opinions are considered in the Discussion . Interviewees were circulated the main report for comments and to confirm that their views were presented accurately . Four provided comments . Findings Severity of the problem Nearly all those interviewed thought that there is a serious shortage of social science research capacity in East Africa , the few really good social scientists being overworked and overwhelmed with requests for collaboration . Most academic health-related social science research in Uganda was said to be run by Northerners , yet Uganda was thought to have stronger capacity than Kenya , with Tanzania coming third . Particular limitations identified were in qualitative research , analysis and writing skills , and health-related specialisms . Interviewees stated that the vast bulk of social science research in East Africa is commissioned by NGOs or government departments , mostly funded from the North ; consequently , it is highly applied and determined by external priorities . The few opportunities for academic research were said to come primarily from Northern researchers who win the funding , resulting in unbalanced collaborations . Research processes : inter-collegiate support Poor social science capacity was primarily related to under-development and global economic inequalities : very poor schooling , talented students choosing high status vocational courses , poor university facilities and teaching , research funded through Northern institutions , and the drain of senior researchers abroad -LRB- Wight , 2005 -RRB- . The problem has been exacerbated by the death of many junior and mid-level Researchers from AIDS -LRB- Pfau & Barton , 2004 , RAWOO , 2002 , Zeleza , 2003 -RRB- . However , the individualised nature of departments and lack of collegiate support were also identified as unhelpful . This was primarily attributed to lack of resources and staff 's reliance on individual research consultancies , resulting in no writing skills training and limited publishing experience to share . A head of department observed that senior staff rarely co-author papers with junior colleagues , due to ` the culture of individualism . ' In her department there was no formal system to support junior researchers , though she was planning a mentoring system . Staff rarely seem to comment on their colleagues ' draft papers ; one senior respondent estimated that at Makerere only 1 % of colleagues would have time . Research processes : consultancies Most of the research work conducted by social scientists in East Africa is in the form of consultancies . The proportion of academics ' time spent on them is unclear -LRB- Kwesiga et al. , 2000 -RRB- , partly perhaps to disguise this from supervisors , but most estimates were around 50 % of working time . Teaching takes up much of the rest , with very little for academic research . ... in Makerere you can spend your entire time just working on very well paid , short-term consultancy studies for NGOs , ... who want something done in three weeks , and will pay you very well ... -LRB- Senior researcher , previously Uganda -RRB- Extremely low university salaries create a powerful incentive for consultancies . A research associate 's salary might be $ 250/month , while consultancies can pay $ 100 -- $ 250/day . In one research institute consultancies augment salaries from around $ 400/month to about $ 5000 . A head of department explained : ` ... to rely on your salary would never make ends meet at all . ' Furthermore , in contrast to regular salaries , most researchers can avoid declaring consultancy fees for tax -LRB- 30 % -RRB- . Research commissioners , predominantly government departments or NGOs , usually seek a contract with individuals , or sometimes consultancy firms , but rarely with university departments . Private consultancy firms , often constituted for a particular brief , usually employ university staff to help with the bid and subsequent research . Commissioning bodies are reportedly unwilling to pay overheads to institutions , and when they do , they are generally very low , e.g. , 5 -- 20 % in Makerere departments , 20 % at the University of Dar es Salaam , and a maximum of 15 % at a Kampala independent research centre . The senior management at Makerere were said to encourage departments to become consulting firms and demand 30 % overheads , but this leads university staff to work independently , undercutting university departments and earning more . The predominance of research consultancies is critical for the development of research capacity . Financial insecurity leads researchers to take on any work available , and consequently : There are no research traditions being developed ... . We are social scientists but very few are specialists ... -LRB- Faculty dean -RRB- Consultancy work also inevitably restricts academics ' time for teaching and supervision . At Dar es Salaam and Makerere consultancies should not interfere with normal academic work , but this is difficult to enforce : He will leave you . And who loses ? This is the person you have trained up to PhD level , and now he is leaving you , and you have no one to teach ... -LRB- Head of department -RRB- Writing consultancy reports provides little incentive to develop analytical skills . Reports generally involve very tight timetables with little opportunity for peers ' critical input , are descriptive and have limited dissemination -LRB- sometimes for internal use only -RRB- . Several researchers said they do not publish from consultancies because they need the funder 's permission , but none knew of it being refused . More plausibly , there is rarely time for such writing . Consequently , the CVs of highly experienced researchers often list numerous consultancy reports but very few journal publications , jeopardising their applications for senior jobs . The conflict between consultancies and academic publications reportedly generates a professional culture in which : ` the point is to try and chase the quick money , and not take advantage of the chance of academic growth ... people do n't value it very much . ' A faculty dean commented : Consultancies is not building the capacity of the person who is doing it . ... . -LSB- Some -RSB- have even refused scholarships to do PhDs because they were busy doing consultancies . Only two interviewees questioned the inevitability that consultancies detract from publications or teaching : ` ... consultancies can ... be a source of writing ... -LSB- and -RSB- training . ' -LRB- Director large research programme -RRB- . The high remuneration from consultancies , and tensions with teaching responsibilities , might encourage researchers to become full-time consultants . However , few do this because commissioners seek the ` recognition and visibility ' of ` high powered people ' in established university posts . Furthermore , it would be too insecure : ` You would earn much more in the short-term , but then you would be unemployed in the long-term . ' Strengthening research capacity and likely barriers Respondents proposed many ideas to strengthen health-related social science research capacity -LRB- see Wight , 2005 -RRB- . Here I focus on those to modify the individualism of research practice and consultancies . Five senior interviewees identified the need to develop writing skills , for instance ` to guide you through ... the very complicated processes ... and requirements ' to publish in international journals . Suggestions included experienced and in-experienced staff co-authoring , mentoring systems and support networks . The director of a research-facilitating NGO advocated posts dedicated to writing support , but with salaries adequate to prevent appointees taking on consultancies . The potential advantages of institutional research consultancies were explored , and in particular establishing a norm of significant overheads , e.g. , 30 % . Everyone approved in principle . Overheads could be used for : libraries , computing and internet access ; department-initiated research ; disseminating reports ; training staff and developing writing skills . Institutional consultancies might facilitate a more collective approach to research and assist management by departmental heads . Furthermore , paying overheads might benefit commissioners since they could require reports to be published , at least in an on-line journal . However , several objections to institutional consultancies were also raised.The culture of institutionalising things is not there . Many think the institution is a barrier to them . And ... the bureaucracy , you know , many people would prefer to have the money in their own accounts ... . -LRB- Head of department -RRB- Researchers anticipated the frustrations of inefficient institutional administrations , with long delays in finalising contracts or being paid . It was feared that , since some universities do not allow departmental bank accounts , the central administration might appropriate funds raised through departmental consultancies . Furthermore , fees would not only have to be shared with the institution , but would have to be declared for tax . Consequently , the director of a large programme thought : ` ... people will just try to get around it . They will get consultancies privately . ' Several interviewees said that commissioning agencies would not ` ... want to pay the institutional fee . ' All the American universities -LSB- have -RSB- institutional overheads , but tell DfID that -LSB- they -RSB- have to be factored in -LSB- in Kampala -RSB- ... : `` Oh , no ! '' ... . How am I supposed to run the project without institutional overheads ? ... they have the mentality that they can do it on the cheap . Africa is poor , but it is not cheap ! -LRB- Director of large programme -RRB- It was also argued that some agencies want to commission specific individual researchers , and that individual consultancies incentivise good work produced on time . Some large donors practice their policies of strengthening institutional capacity by only contracting research through institutions , e.g. , the Carnegie and Rockefeller Foundations , the World Bank , and the Swedish and Norwegian development agencies . However , some interviewees thought a concordat with all commissioning agencies to pay minimum overheads would be unrealistic , since East Africa is too dependent on donors . Discussion Although most respondents were Ugandan , the data from Kenya and Tanzania suggest that these findings apply across East Africa , while the broader literature -LRB- e.g. , Carlsson & Wohlgemuth , 1996 ; Sall , 2003 ; Zeleza , 2003 -RRB- and contacts with researchers elsewhere suggest they are relevant to much of sub-Saharan Africa . There is a serious shortage of health-related social science research capacity in this region , as evidenced by the Northern intellectual leadership of most academic research . This perpetuates ` the international intellectual division of labour whereby African ... social scientists ... import appropriate ... theory and , at best , export empirical data . ' -LRB- Zeleza , 2003 , p. 111 -RRB- African countries ' limited ability to define for themselves their problems and the solutions may have very practical consequences . For instance , Cleland and Watkins -LRB- 2006 , p. 2 -RRB- argue that Africans ' frustratingly slow response to the HIV epidemic is because ` the problem , and the remedies , were socially constructed in the West ... . ' Like most previous studies , this one points to global economic inequalities as the primary cause of limited research capacity . However , unremarked in nearly all the published literature , these findings also suggest that the problem is perpetuated by the highly individualised character of research in East Africa , fuelled by the dominance of individually-contracted consultancies . ` Most of our social scientists are not institution based , whether NGO or private . They are there for hire . ' -LRB- Faculty dean -RRB- Such consultancies seem to stunt research capacity : reports are generally not disseminated , thus not contributing to collective understandings , university departments are denied overheads , and staff are diverted from teaching , supporting colleagues , or publishing . Furthermore , consultancies exacerbate the narrow policy orientation of African social science research -LRB- Allen , 1986 ; Rossi , 2004 ; Sall , 2003 -RRB- . Given their prominence , this study explored the potential for research consultancies to be used to strengthen research capacity , which to date has been largely ignored in the wider literature . The principle that consultancies should be contracted with institutions , rather than individuals , with overheads of around 30 % , was widely accepted . This could fund many initiatives to strengthen research capacity , facilitate a more collective approach to research , and in the longer term might mean commissioning agencies get better value . Some African universities and research centres already regulate the division of consultancy fees between researchers and their institution , e.g. , the University of KwaZulu-Natal and the REACH Trust , Malawi -LRB- Theobald & Nhlema , in press -RRB- . However , established individual consultants would probably oppose institutionalisation , given very low university salaries and lack of confidence in departmental administration , due to experience of patronage , mismanagement and corruption -LRB- Zeleza , 2003 -RRB- . Furthermore , commissioning agencies were said to prefer individual consultancies as cheaper and more straightforward . By and large , initiatives to strengthen research capacity do not address the issue of research consultancies , although in practice they are in competition for researchers ' commitment . This was clear in an academic research centre sponsored by an international NGO where researchers are prohibited from consultancy work . However , as noted above , some large donors further the development of institutional capacity by only contracting research through institutions , not individuals . Unsurprisingly , respondents ' accounts were shaped by their professional and institutional positions , for instance leading them to defend their staff or externalise problems -LRB- see Wight , 2005 -RRB- . African interviewees gave more emphasis to economic factors , research commissioners ' restrictions and exclusion from Northern-dominated academic networks , while Northern interviewees were more likely to contrast East African with Northern professional cultures . However , these cultural differences were usually attributed to underlying structural/economic factors . Only one interviewee , an African , explicitly attributed inadequate research capacity to a global economy of academic research , in which Northern institutions actively maintain their dominance . Notably , the most critical reports of East African research came through informal conversations , rather than recorded interviews . This has only been an exploratory study . Further research needs to clarify : the scale of individual consultancies across East Africa ; whether revising commissioning practices would seriously contribute to research capacity ; and , hardly represented here , the views of agencies commissioning consultancies . While the underlying causes of poor research capacity require global economic reform , this study also points to the importance of individually contracted research consultancies in perpetuating the problem . Although they greatly augment meagre university salaries , they also seem to divert university staff from academic research and training the next generation of researchers , stunt the institutional capacity of university departments , restrict the sharing of research findings and perpetuate donors ' control of the research agenda . Commissioning bodies committed to strengthening research capacity should consider devising research contracts , and means to improve university administration , that ameliorate rather than exacerbate the problem .

O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O

research capacity
research consultancies

sub-saharan africa
health social sciences
knowledge economy
east african universities


Are radiographs needed when MR imaging is performed for non-acute knee symptoms in patients younger than 45 years of age ? Objective The objective was to determine the value of radiographs in young adults with non-acute knee symptoms who are scheduled for magnetic resonance imaging -LRB- MRI -RRB- . Introduction Radiographs in patients with acute knee problems that are obtained at , or close to , the time of trauma serve mainly to exclude fractures and most of these radiographs are normal . To reduce the total number , and especially the number of normal radiographs , clinical decision rules that identify patients with a high risk of fracture have been developed and validated -LSB- 2 -- 4 -RSB- . In patients with non-acute knee symptoms radiographs are the mandatory minimal initial exam in patients with non-traumatic knee pain , according to ACR appropriateness criteria -LSB- 5 -RSB- . Magnetic resonance imaging -LRB- MRI -RRB- is frequently obtained if additional imaging is clinically needed to search for suspected intra-articular abnormalities . The value of radiographs relative to MRI in a heterogeneous group of patients was recently reported -LSB- 6 -RSB- . Radiographs were rated `` essential '' or `` very important '' in 46 -- 58 % of cases and added `` not needed information '' in 14 -- 29 % of cases . However , the value of radiographs relative to MRI in young adults presenting with non-acute knee symptoms has , to our knowledge , not been established . If in these patients radiographs could be omitted , or obtained only when needed when reading MRI , this could possibly lead to a significant reduction of the volume of knee radiographs with ensuing reduction in radiation dose and costs . The purpose of our prospective study was to determine the value of radiographs in young patients with non-acute knee symptoms and suspected intra-articular pathology who are scheduled for MRI based on the results of a physical exam . We therefore determined the prevalence of osseous abnormalities visible on radiographs and MRI and the yield of MRI compared with that of radiographs . In addition , we measured the radiation dose of standard radiographs of the knee . Material and methods Over 3 years , 961 patients referred from general practitioners to the outpatient surgery or orthopedic surgery clinics of three hospitals -LRB- two general hospitals and one university hospital -RRB- because of non-acute knee symptoms agreed to participate in our prospective study . The symptoms had to have been present for at least 4 weeks . The institutional review board of each hospital approved the study . We obtained written informed consent from all patients . At study entry a standardized history , including inventory of traumatic events and other knee-related events such as morbidity and medical procedures was taken . Physical exam was performed by one of 15 -LRB- orthopedic -RRB- surgeons or by residents under their supervision . All the patients included underwent MRI and radiographs of the knee . Recent radiographs taken for the same complaints that were obtained prior to study inclusion were not repeated . We included patients who met the following inclusion criteria : knee symptoms -LRB- pain , swelling of the joint , feeling of instability or giving way , history of locking -RRB- of at least 4 weeks ' duration and age between 16 and 45 years . To obtain a homogenous study population without co-morbidity we did not include patients who had had previous surgery of the affected knee -LRB- including arthroscopy -RRB- or previous MRI , a history of rheumatoid arthritis , and clinical diagnosis of retropatellar chondromalacia , contra-indication for MRI , or an incomplete data set . One hundred and sixty-three patients -LRB- 17.0 % -RRB- were eventually excluded -LRB- Table 1 -RRB- , leaving 798 patients as our study group . Of these excluded patients a substantial number should not have been included by the orthopedic surgeons in the first place according to our study protocol , for instance , because they were either too young , too old or had knee complaints of less than 4 weeks ' duration . Table 1Excluded patients . Of the 961 patients referred , 163 -LRB- 17.0 % -RRB- were excludedExclusion criterianSymptoms of less than 4 weeks ' duration65Aged under 16 years1Aged over 45 years6Previous surgery8Retropatellar chondromalacia14Previous MRI1Radiographs unavailable or not obtained65MRI or arthroscopy prohibited2Immediate arthroscopy required30Criteria are not mutually exclusive . One out of six musculoskeletal radiologists -LRB- all with at least 5 years ' experience -RRB- evaluated the radiographs without knowledge of the MR images and recorded their findings on a Case Record Form -LRB- CRF -RRB- . The radiation dose of standard antero-posterior and lateral radiographs was determined in two of the three hospitals using flat ionization chambers . We used PCXMC software -LRB- STUK , Finland -RRB- to convert the measured radiation doses into effective doses . The radiologist evaluated the radiographs for articular surface lesions , using the classification developed by Bohndorf -LSB- 7 -RSB- . Osteoarthritis was scored using the scoring system developed by Kellgren et al. -LSB- 1 -RSB- . In the analysis , grades 1 to 3 were considered as one group , with osteoarthritis being present . Radiographs were also evaluated for fractures -LSB- 8 -- 10 -RSB- , loose bodies , and incidental findings . A loose body was defined as a radiodense circumscriptive lesion located in the femorotibial , patellofemoral jointline or suprapatellar pouch . Incidental findings , such as non-ossifying fibromas and enchondromas were diagnosed using established criteria -LSB- 11 , 12 -RSB- . On radiographs a lesion was considered a non-ossifying fibroma if it met the following criteria : asymptomatic , cortical metaphyseal location , and radiographically non-aggressive . A lesion was considered an enchondroma if it met the following criteria : central metaphyseal location , chondroid matrix , geographic pattern of destruction with or without sclerotic margin . We performed the MR studies in all three hospitals on an identical 0.5-T system -LRB- Gyroscan T5 , Philips Medical Systems , Best , the Netherlands -RRB- , with the same software release using a dedicated transmit -- receive knee coil . The standardized scanning protocol consisted of three sequences : a sagittal and a coronal dual spin-echo -LRB- SE -RRB- sequence and a sagittal T1-weighted 3D gradient-echo -LRB- GE -RRB- sequence with frequency selective fat suppression . The following parameters were identical for both SE sequences : field of view 140 -- 160 mm , echo time -LRB- TE -RRB- 20/80 ms. The coronal dual SE had a repetition time -LRB- TR -RRB- of 2,100 ms , a 256 × 205 matrix and a slice thickness of 5 mm with a 0.5-mm interslice gap . The sagittal dual SE had a TR of 2,350 ms , a 256 × 179 matrix and a slice thickness of 4 mm with a 0.4-mm interslice gap . The parameters for the sagittal frequency selective fat-suppressed T1-weighted 3D GE were : TR 70 ms , TE 13 ms , 45 ° flip angle , field of view 160 mm , 256 × 205 matrix , 4 mm slice thickness with a 2-mm overlap . The total imaging time of the standard protocol -LRB- including the initial survey sequence -RRB- was 26 min . After reading the radiographs one out of six radiologists evaluated MR images and reported his findings on a CRF . In accordance with usual management the observer had access to the radiographs , but not to the reports , when evaluating MR images . The CRF was similar to the one used for radiographs -LSB- 8 -- 12 -RSB- , except that bone marrow edema was added as an item -LSB- 13 -RSB- . For articular surface lesions we again used the classification developed by Bohndorf -LSB- 7 -RSB- . For osteoarthritis we used the scoring system developed by Recht et al. -LSB- 14 -RSB- . For the purpose of this study , grades 1 to 4 were considered as one group , with osteoarthritis being present . To overcome bias in the reading of MR studies , introduced by knowledge of the results of conventional radiographs , one radiologist -LRB- JLB -RRB- re-evaluated MR studies of patients with abnormalities on conventional radiographs with the exception of osteoarthritis of Kellgren -LSB- 1 -RSB- grades 1 -- 2 . We used the same CRF format . At this second evaluation , MR studies of patients with osseous abnormalities on conventional radiographs were mixed with age - and gender-matched MR studies of patients without abnormalities on conventional radiographs . The radiographs and the findings on the CRF were not available at that time . We divided the completed CRFs over two groups : group A had no history of trauma , and group B had a history of trauma of more than 4 weeks before presentation at the hospital . We used the Chi-squared test to identify significant differences between the yield of radiographic and MR diagnoses , and between the number of findings in group A and that in group B. To look for statistically significant differences between the yield of radiographs and MRI within groups A , B and the study population as a whole , we used McNemar 's Chi-squared test . Results The median age of the 798 patients included was 31 years -LRB- range 16 -- 45 years -RRB- , and 261 patients -LRB- 32.7 % -RRB- were female . Minimal and median duration of symptoms were 4 and 20 weeks respectively -LRB- range 4 -- 1,490 weeks -RRB- . Three hundred and thirty-two patients reported no history of trauma -LRB- group A -RRB- , and 466 patients reported an old -LRB- more than 4 weeks prior to consultation -RRB- history of trauma -LRB- group B -RRB- . Magnetic resonance imaging depicted arthroscopically treatable intra-articular pathology in 341 patients -LRB- 42.7 % -RRB- . Medial and lateral meniscal tears were found in 225 -LRB- 28.2 % -RRB- and 111 patients -LRB- 13.9 % -RRB- respectively . The average radiation dose of supine antero-posterior and lateral radiographs was 0.2 and 0.3 mSv respectively . The median duration of the interval between radiographs and MRI was 8 days -LRB- 95 percentile , 85 days -RRB- . In 196 patients -LRB- 24.6 % -RRB- radiographs were obtained prior to inclusion in the study . These radiographs were not repeated since the knee complaints had not changed between the moment they were obtained and inclusion in this study . In group A , radiographs showed 36 osseous abnormalities in 332 patients -LRB- 10.8 % , Table 2 -RRB- . All these abnormalities , except 13 Kellgren -LSB- 1 -RSB- grade 1 osteoarthritis cases , were also depicted on MRI . There were 23 concordant radiographic and MRI diagnoses -LRB- Fig. 3 ; Table 2 -RRB- . One incidental finding -LRB- enchondroma -RRB- was demonstrated on radiographs and MRI . The majority of the 72 diagnoses made only with MRI were osteoarthritis and bone bruising -LRB- Table 2 -RRB- . Most osseous lesions -LRB- osteoarthritis , articular surface lesions , loose bodies and bone marrow edema -RRB- with the exception of incidental findings -LRB- one case -RRB- and old fractures -LRB- not present in this group -RRB- were significantly more often diagnosed with MRI than with radiographs -LRB- Table 2 -RRB- . Table 2Osseous abnormalities detected on radiographs only , on radiographs and MRI , and on MRI only in 332 patients with non-acute non-traumatic knee complaintsOsseous abnormalityR -LRB- % -RRB- R and MR -LRB- % -RRB- MRI -LRB- % -RRB- Total -LRB- % -RRB- McNemar test , p valueOA13 -LRB- 3.9 -RRB- 18 -LRB- 5.4 -RRB- 39 -LRB- 11.7 -RRB- 70 -LRB- 21.1 -RRB- 0.00 ASL0 -LRB- 0 -RRB- 3 -LRB- 0.9 -RRB- 7 -LRB- 2.1 -RRB- 10 -LRB- 3.0 -RRB- 0.02 LB0 -LRB- 0 -RRB- 1 -LRB- 0.3 -RRB- 6 -LRB- 1.8 -RRB- 7 -LRB- 2.1 -RRB- 0.03 Fractures0 -LRB- 0 -RRB- 0 -LRB- 0 -RRB- 0 -LRB- 0 -RRB- 0 -LRB- 0 -RRB- NAIncidental finding0 -LRB- 0 -RRB- 1 -LRB- 0.3 -RRB- 0 -LRB- 0.0 -RRB- 1 -LRB- 0.3 -RRB- 1.00 Bone marrow edema0 -LRB- 0 -RRB- 0 -LRB- 0 -RRB- 20 -LRB- 6.0 -RRB- 20 -LRB- 6.0 -RRB- NA Total13 -LRB- 3.9 -RRB- 23 -LRB- 6.9 -RRB- 72 -LRB- 21.7 -RRB- 108 -LRB- 32.5 -RRB- 0.00 OA : osteoarthritis grade 1 or higher according to Kellgren -LSB- 1 -RSB- on radiographs and according to Recht -LSB- 14 -RSB- on MRI ; ASL : articular surface lesion with or without disrupted cartilage ; LB : loose body ; R : abnormality detected with radiographs only ; R and MR : abnormality detected with both radiograph and MRI ; MRI : abnormality detected with MRI only ; NA : not applicable . Categories are not mutually exclusive . In group B , radiographs showed 40 osseous abnormalities in 466 patients -LRB- 8.6 % , Table 3 -RRB- . All these abnormalities , except 15 Kellgren -LSB- 1 -RSB- grade 1 osteoarthritis cases , were also depicted on MRI . There were 25 concordant radiographic and MRI diagnoses -LRB- Figs. 1 , 4 , 5 and 6 ; Table 3 -RRB- . Four of the six incidental findings were diagnosed on radiographs and MRI -LRB- 1 non-ossifying fibroma and 3 enchondromas , Fig. 7 -RRB- . Two enchondromas were depicted on MRI only -LRB- Fig. 8 -RRB- . The majority of the 192 diagnoses made only with MRI were bone marrow edema -LRB- Fig. 2 -RRB- , osteoarthritis and articular surface lesions -LRB- Table 3 -RRB- . These three diagnoses were significantly more often diagnosed with MRI than with radiographs -LRB- Table 3 -RRB- . There was no significant difference between MRI and radiographs in the diagnosis of loose bodies , old fractures and incidental findings . Table 3Osseous abnormalities detected on radiographs only , on radiographs and MRI , and on MRI only in 466 patients with non-acute traumatic knee complaintsOsseous abnormalityR -LRB- % -RRB- R and MR -LRB- % -RRB- MRI -LRB- % -RRB- Total -LRB- % -RRB- McNemar test , p valueOA15 -LRB- 3.2 -RRB- 13 -LRB- 2.8 -RRB- 65 -LRB- 13.9 -RRB- 93 -LRB- 20.0 -RRB- 0.00 ASL0 -LRB- 0 -RRB- 3 -LRB- 0.6 -RRB- 22 -LRB- 4.7 -RRB- 25 -LRB- 5.4 -RRB- 0.00 LB0 -LRB- 0 -RRB- 1 -LRB- 0.2 -RRB- 4 -LRB- 0.9 -RRB- 5 -LRB- 1.1 -RRB- 0.13 Fractures0 -LRB- 0 -RRB- 4 -LRB- 0.9 -RRB- 3 -LRB- 0.6 -RRB- 7 -LRB- 1.5 -RRB- 0.25 Incidental finding0 -LRB- 0 -RRB- 4 -LRB- 0.9 -RRB- 2 -LRB- 0.4 -RRB- 6 -LRB- 1.3 -RRB- 0.5 Bone marrow edema0 -LRB- 0 -RRB- 0 -LRB- 0 -RRB- 96 -LRB- 20.6 -RRB- 96 -LRB- 20.6 -RRB- NA Total15 -LRB- 3.2 -RRB- 25 -LRB- 5.4 -RRB- 192 -LRB- 41.2 -RRB- 232 -LRB- 49.8 -RRB- 0.00 Categories are not mutually exclusive.Fig . 1Severe osteoarthritis on both radiographs and MRI . a , b Lateral and antero-posterior radiographs showing deformation of the femoral condyles and tibia plateau with marked subchondral cyst formation and osteophyte formation in a 44-year-old female patient with a history of knee trauma -LRB- group B -RRB- . c -- e Coronal proton density and T2-weighted spin-echo -LRB- SE -RRB- images and of the same lesion showing , in addition to the deformities and changes already noted on the radiographs , the osteochondral defect to a better extent . e Sagittal T2-weighted SE image showing the same features , but also focal full-thickness cartilage lossFig . 2Three-month-old transchondral fracture on both radiographs and MRI . a , b Antero-posterior and lateral radiograph showing irregularity and deformation of the lateral femoral condyle consistent with a transchondral fracture of the lateral femoral condyle in a 40-year-old male with a history of knee trauma -LRB- group B -RRB- . c -- d Sagittal T2-weighted SE images and T1-weighted 3D gradient-echo -LRB- GE -RRB- with fat suppression showing subtle contour deformity of the lateral femoral condyle with kissing bone bruises in the lateral femoral condyle and tibial plateau Osseous abnormalities were more frequently encountered in group B than in group A -LRB- p < 0.001 -RRB- . This difference is explained by a significant difference in the number of old fractures -LRB- p < 0.05 , no old fractures were seen in group A -RRB- , and patients with bone marrow edema -LRB- p < 0.001 -RRB- . Bone marrow edema was demonstrated with MRI in 116 patients -LRB- 14.5 % , Table 4 -RRB- ; 96 of these were found in group B -LRB- 82.8 % of patients with bone marrow edema , Table 3 -RRB- . Table 4Osseous abnormalities detected on radiographs only , on radiographs and MRI , and on MRI only in 798 patients with non-acute knee complaintsOsseous abnormalityR -LRB- % -RRB- R and MRI -LRB- % -RRB- MRI -LRB- % -RRB- Total -LRB- % -RRB- McNemar test , p valueOA28 -LRB- 3.5 -RRB- 31 -LRB- 3.9 -RRB- 104 -LRB- 13.0 -RRB- 163 -LRB- 20.4 -RRB- 0.00 ASL0 -LRB- 0 -RRB- 6 -LRB- 0.8 -RRB- 29 -LRB- 3.6 -RRB- 35 -LRB- 4.4 -RRB- 0.00 LB0 -LRB- 0 -RRB- 2 0.3 -RRB- 10 -LRB- 1.3 -RRB- 12 -LRB- 1.5 -RRB- 0.00 Fractures0 -LRB- 0 -RRB- 4 -LRB- 0.53 -LRB- 0.4 -RRB- 7 -LRB- 0.9 -RRB- 0.25 Incidental finding0 -LRB- 0 -RRB- 5 -LRB- 0.6 -RRB- 2 -LRB- 0.3 -RRB- 7 -LRB- 0.9 -RRB- 0.5 Bone marrow edema0 -LRB- 0 -RRB- 0 -LRB- 0 -RRB- 96 -LRB- 12.0 -RRB- 96 -LRB- 12.0 -RRB- NATotal28 -LRB- 3.5 -RRB- 48 -LRB- 6.0 -RRB- 264 -LRB- 33.1 -RRB- 340 -LRB- 42.6 -RRB- 0.00 Categories are not mutually exclusive . In 6 -LRB- 30 % -RRB- of the 20 group A patients with bone marrow edema , it was either associated with intra-articular damage of non-osseous origin or it was an isolated finding . The associated osseous abnormalities in the other 14 patients were as follows : bone marrow edema was found in 4 of the 10 patients with articular surface lesions , in 1 of the 7 patients with a loose body , and in 9 of the 70 patients with osteoarthritis . In 89 -LRB- 92.7 % -RRB- of the 96 group B patients with bone marrow edema , it was either associated with intra-articular damage of non-osseous origin or it was an isolated finding . The associated osseous abnormalities in the other 7 patients were as follows : bone marrow edema was found in 4 of the 25 patients with articular surface lesions -LRB- Fig. 2 -RRB- , in 1 of the 5 patients with a loose body and in 2 of the 93 patients with osteoarthritis . In our population we did not find any other osseous lesions like osteopenia or femoropatellar disease . Also , we did not find chondrocalcinosis on radiographs . Subsequently , all patients with radiographically detected abnormalities with the exception of Kellgren -LSB- 1 -RSB- grade 1 and 2 osteoarthritis were identified . MRI studies of the 17 patients with 18 radiographically detected osseous abnormalities were mixed with 17 gender - and age-matched MRI studies of patients without abnormalities on radiographs . There were 6 females in each group , and the mean age in each group was 33.1 years , SD 7.9 years -RRB- . At revision , the reader -LRB- JLB -RRB- was blinded to all information and had no access to the radiographs . All 18 osseous abnormalities -LRB- 1 caae of osteoarthritis Kellgren grade 3 -LSB- Fig. 1 -RSB- , 6 articular surface lesions -LSB- Figs. 2 , 3 -RSB- , 2 loose bodies -LSB- Fig. 4 -RSB- , 4 old healed fractures -LSB- Figs. 5 , 6 -RSB- and 5 incidental findings -LSB- 4 enchondromas and 1 non-ossifying fibroma , Figs. 7 , 8 -RSB- -RRB- were all diagnosed on MRI . Fig. 3Twenty-six-month-old transchondral fracture on both radiographs and MRI . a Antero-posterior radiograph showing abnormal density , subtle irregularity and deformation of the medial femoral condyle in a 35-year-old male patient with no history of knee trauma -LRB- group A -RRB- . b -- d Sagittal T1-weighted 3D GE with fat suppression and coronal proton density and T2-weighted SE images of this knee showing the transchondral fractureFig . 4Loose body on both radiography and MRI . a Lateral radiograph showing a ventrally located loose body in the left femorotibial joint in an 18-year-old male professional skater with a history of knee trauma -LRB- group B -RRB- . b -- c Sagittal T1-weighted 3D GE with fat suppression and coronal proton density SE images of the same patient , also showing the loose body that is ventrally located in the lateral compartment of the femorotibial joint . At subsequent arthroscopy this loose body was removedFig . 5Eight-month-old healed fracture on both radiograph and MRI . a Lateral radiograph showing a healed fracture of the inferior patellar pole in an 18-year-old male patient with a history of knee trauma -LRB- group B -RRB- . b Sagittal proton density SE image of the same patient , also delineating the healed fracture of the inferior pole of the patellaFig . 6Two-month-old healing fracture on both radiograph and MRI . a Lateral radiograph showing a healing fracture of the left inferior patellar pole in a 40-year-old male patient with a history of knee trauma -LRB- group B -RRB- . b , c Sagittal T1-weighted 3D GE with fat suppression and T2-weighted SE images of the same patient , also delineating the healing fracture of the inferior pole of the patella without cartilaginous irregularities . Around the fracture line bone marrow edema can be appreciatedFig . 7Incidental finding depicted on both radiographs and MRI . a , b Lateral and antero-posterior radiographs showing a central , metaphyseally located lesion with chondroid matrix consistent with enchondroma in the femur in a 44-year-old female patient with a history of knee trauma -LRB- group B -RRB- . c , d Sagittal proton density and T2-weighted SE images of the same lesionFig . 8Incidental finding depicted on MRI only . a Lateral radiograph showing no femoral osseous lesion in a 40-year-old female patient with a history of knee trauma -LRB- group B -RRB- . b , c Sagittal proton density and T2-weighted SE images showing a metaphyseal lesion consistent with an enchondroma Discussion Key characteristics of our population such as age , gender , clinical suspicion of intra-articular abnormalities , intra-articular abnormalities detected with MRI , and history suggest that our conclusions can be applied to typical populations scheduled for MRI to analyze non-acute knee problems . The yield of radiographs in patients with subacute or chronic knee symptoms who are otherwise healthy and who are scheduled for MRI based on the results of a physical exam suggesting the presence of intra-articular damage is only 9.5 % -LRB- 76 patients -RRB- . The majority of these patients -LRB- 77.6 % -RRB- have osteoarthritis . We failed to confirm with MRI the radiographic diagnosis of Kellgren -LSB- 1 -RSB- grade 1 osteoarthritis in 28 patients , but none of the other abnormalities were diagnosed only with radiographs . This was confirmed in a second reading of MRI blinded to clinical and radiographic information . Radiographs do not , in the setting of this study , contribute to clinical decision-making or clinical management of the patient . Although the dose administered when obtaining radiographs of the knee is small , the size of the population with knee complaints make the reduction of an administered dose a relevant issue . Radiographs can therefore be omitted in this specific population when the decision to perform MRI is taken based on clinical assessment . The disadvantage of occasionally missing Kellgren -LSB- 1 -RSB- grade 1 osteoarthritis is limited when we realize that because of the lack of a gold standard these radiographic diagnoses may also be false-positive . Taljanovic et al. -LSB- 6 -RSB- rated radiographs as `` essential '' or `` very important '' in 46 -- 58 % of cases and radiographs added `` not needed information '' in 14 -- 29 % of cases . They conclude in their study that radiographs are an important , and sometimes essential initial , complementary study for reading musculoskeletal MR examinations . This apparently different conclusion can be explained by the differences in study populations . Taljanovic et al. -LSB- 6 -RSB- analyzed a large variety of diagnosis -LRB- trauma , infection , tumors , degenerative or miscellaneous -RRB- in all anatomical locations in patients of all ages . We only analyzed patients between 16 and 45 years of age with non-acute knee symptoms lasting at least 4 weeks , excluding amongst others patients with acute knee symptoms -LRB- i.e. , less than 4 weeks -RRB- , history of rheumatoid arthritis , and clinical diagnosis of retropatellar chondromalacia . Other major methodological differences are mainly related to this difference . The concordance between radiographs and MRI is not high because of the large number of diagnoses -LRB- 77.6 % -RRB- made only with MRI . In groups A and B osteoarthritis , articular surface lesions , and bone marrow edema were significantly more often diagnosed with MRI than with radiographs . Loose bodies were significantly more frequently diagnosed with MRI in group A only . This higher yield of MRI is no surprise , since abnormalities such as articular surface lesions and bone marrow edema are known to be better , or even exclusively appreciated on MRI . These findings have , in addition to the intra-articular abnormalities detected with MRI , potential clinical significance in view of the patients ' presenting symptoms . The advantage and comprehensiveness of MRI is illustrated by its ability to demonstrate bone marrow edema that is associated with other abnormalities . In the patients with a history of old trauma , bone marrow edema was mainly -LRB- 92.7 % -RRB- associated with intra-articular damage . In the group with no history of trauma , however , bone marrow edema was mainly -LRB- 70 % -RRB- seen in association with osseous abnormalities , thus facilitating the diagnosis of articular surface lesions and osteoarthritis . This prospective study has several limitations that are mainly related to the decision to follow usual care . This means that radiographs were available at the time of MRI . To overcome this limitation , one radiologist -LRB- JLB -RRB- re-evaluated MR studies of patients with abnormalities on conventional radiographs without knowledge of the radiographs , as described . Another limitation is that we could not determine accuracy because of the absence of a reference standard . If we look at the discordant cases , there are no potentially false-negative MRI diagnoses -LRB- with the exception of Kellgren -LSB- 1 -RSB- grade 1 osteoarthritis -RRB- , but the number of potential false-positive MRI diagnoses -LRB- abnormal finding on MRI in combination with a normal radiograph -RRB- is substantial , mainly because of the high prevalence of bone marrow edema . Another possible limitation of this study is the selection bias introduced by including only patients between 16 and 45 years of age and excluding patients with co-morbidity . The study design was not tailored toward assessment of the value of conventional radiographs only . The overall goal of this multicenter study was to evaluate the efficacy of MRI compared with direct arthroscopy in patients with subacute knee complaints , based on clinical outcome . To this end we tried to obtain a homogenous study population without co-morbidity . This is most likely the reason we encountered only 1 patient with high-grade osteoarthritis -LRB- Kellgren -LSB- 1 -RSB- grade 3 -RRB- . However , because the majority of MR examinations performed in our institutions will be of patients in this age range without known co-morbidity , we do not think this selection bias will alter our overall conclusions . We tried to mimic usual care as much as possible in this study . However , in our study MRI was performed within 2 weeks of inclusion in the study . Due to the limited availability of MRI compared with conventional radiographs in most hospitals , MRI often can not be performed at such short notice . This can lead to a considerable waiting time for MR examinations and this may direct physicians to prior conventional radiographs to rule out gross pathology and reassure the patient . To prevent these unnecessary radiographs , the waiting time for MRI must be as short as possible . In the Netherlands waiting times for MRI in most institutions are down from several months a couple of years ago to several weeks nowadays . We conclude that radiographs should not be obtained routinely when MRI is being performed in non-acute young patients with knee complaints because the number of clinically relevant lesions detected on radiographs is low . In addition , the small number of abnormalities found on radiographs is , with the exception of an occasional case of Kellgren -LSB- 1 -RSB- grade 1 osteoarthritis , also depicted on MRI . Reduction of costs and radiation dose is small in the individual patient , but , because of its size , substantial in the entire population with subacute and chronic complaints suspected to be knee injury .

O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O B I I O O O O O B O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O B O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O

knee
magnetic resonance imaging
radiographs


Maximum

tumor

diameter

is

not

an

independent

prognostic

factor

in

high-risk

localized

prostate

cancer

Objectives

Previous

studies

suggest

that

maximum

tumor

diameter

-LRB-

MTD

-RRB-

is

a

predictor

of

recurrence

in

prostate

cancer

-LRB-

PC

-RRB-

This

study

investigates

the

prognostic

value

of

MTD

for

biochemical

recurrence

-LRB-

BCR

-RRB-

in

patients

with

PC

after

radical

prostatectomy

-LRB-

RP

-RRB-

with

emphasis

on

high-risk

localized

prostate

cancer

Introduction

The

characteristics

mostly

used

to

predict

progression

of

prostate

cancer

-LRB-

PC

-RRB-

after

radical

prostatectomy

-LRB-

RP

-RRB-

are

Gleason

score

pre-operative

PSA

level

pathological

staging

positive

surgical

margins

and

tumor

volume

-LRB-

TV

-RRB-

-LSB-

-RSB-

The

first

three

are

also

used

to

define

high-risk

localized

PC

-LSB-

-RSB-

TV

in

the

RP

specimen

is

also

clearly

associated

with

prognosis

However

whether

it

is

an

independent

prognostic

factor

both

for

the

total

group

and

for

the

high-risk

group

still

remains

controversial

-LSB-

-RSB-

Epstein

et

al.

-LSB-

-RSB-

stated

that

although

TV

is

a

predictor

of

progression

it

did

not

provide

additional

information

over

Gleason

score

and

pathological

stage

This

was

also

found

in

a

study

by

Salomon

et

al.

-LSB-

-RSB-

where

only

Gleason

score

and

pathological

stage

were

independent

factors

to

predict

progression

after

RP

If

these

parameters

were

known

TV

did

not

provide

any

additional

information

This

is

in

contrast

with

Stamey

et

al.

-LSB-

-RSB-

who

found

that

TV

is

an

independent

prognostic

parameter

for

PC

progression

These

findings

were

also

observed

in

other

studies

-LSB-

-RSB-

of

these

studies

however

specifically

addressed

the

high-risk

subgroup

An

explanation

of

these

conflicting

results

might

be

that

TV

estimations

can

be

done

with

the

help

of

several

techniques

as

Humphrey

and

Volmer

-LSB-

-RSB-

described

earlier

Moreover

these

techniques

are

rather

complex

and

time-consuming

Therefore

maximum

tumor

diameter

-LRB-

MTD

-RRB-

has

been

suggested

as

a

fast

and

easy

proxy

for

TV

Renshaw

et

al.

-LSB-

-RSB-

noted

that

simple

measurements

of

the

largest

diameter

of

the

largest

tumor

from

glass

slides

is

a

predictor

of

PSA

failure

This

was

supported

by

Eichelberger

et

al.

-LSB-

-RSB-

who

showed

that

MTD

correlates

with

TV

and

other

potential

prognostic

factors

for

clinical

outcome

However

these

studies

had

either

a

small

number

of

patients

with

a

relatively

short

follow-up

-LRB-

patients

median

follow-up

months

-RRB-

or

did

not

investigate

the

correlation

between

MTD

and

biochemical

recurrence

-LRB-

BCR

-RRB-

Therefore

in

this

present

study

with

a

large

cohort

of

RP

specimens

and

a

median

follow-up

of

months

we

studied

the

prognostic

value

of

MTD

as

a

surrogate

for

tumor

volume

for

BCR

in

patients

with

PC

with

special

attention

to

the

high-risk

group

Materials

and

methods

Between

and

patients

were

treated

with

RP

for

clinically

localized

PC

at

our

institute

Of

these

patients

were

excluded

from

analyses

because

of

HIFU

treatment

hormonal

pre-treatment

or

irradiation

before

RP

Of

the

remaining

patients

five

had

incomplete

follow-up

data

Charts

were

examined

retrospectively

for

clinical

follow-up

data

and

risk

group

classification

These

risk

groups

were

classified

according

to

D'Amico

et

al.

-LSB-

-RSB-

High

risk

was

defined

as

stage

or

PSA

level

ng/ml

or

Gleason

score

and

we

formed

one

group

of

the

low

and

intermediate

risk

group

-LRB-

stage

PSA

level

ng/ml

and

Gleason

score

-RRB-

All

RP

specimens

were

fixed

overnight

inked

and

cut

into

serial

transverse

mm

thick

slices

according

to

a

standard

protocol

by

Ruijter

et

al.

-LSB-

-RSB-

In

brief

the

apical

and

basal

margins

were

amputated

to

a

thickness

of

mm

and

sectioned

parasagittally

at

mm

intervals

The

seminal

vesicles

were

sectioned

parallel

and

entirely

submitted

The

prostate

was

then

sectioned

perpendicularly

to

the

long

axis

-LRB-

apical

to

basal

-RRB-

of

the

gland

along

the

posterior

rectal

surface

at

intervals

Tumor

was

outlined

on

the

microscopic

glass

slides

and

schematically

drawn

on

the

macroscopically

photographed

transverse

sections

in

order

to

be

able

to

reconstruct

tumor

extension

and

tumor

multifocallity

Detailed

pathological

analysis

including

number

of

tumors

total

volume

of

all

tumors

MTD

pathological

staging

Gleason

score

extracapsular

extension

and

positive

margins

was

performed

by

a

single

pathologist

-LRB-

CAHK

-RRB-

Tumors

were

staged

using

the

American

Joint

Committee

on

Cancer

-LRB-

AJCC

-RRB-

TNM

staging

criteria

of

-LSB-

-RSB-

MTD

was

defined

as

the

largest

diameter

of

the

largest

tumor

MTD

was

determined

by

marking

both

ends

of

the

tumor

and

measuring

the

distance

at

the

glass

slide

directly

If

the

tumor

was

present

on

consecutive

glass

slides

thickness

of

the

slices

of

the

concerning

sections

was

summed

This

reconstructed

diameter

was

considered

as

MTD

if

it

was

larger

than

the

diameter

and

was

visualized

directly

on

the

glass

slides

PSA

values

were

obtained

before

surgery

and

at

every

follow-up

point

BCR

after

RP

was

defined

as

two

subsequent

PSA

levels

above

ng/ml

among

patients

who

reached

non-measurable

levels

after

RP

Statistical

analysis

Baseline

characteristics

are

summarized

with

median

and

interquartile

ranges

-LRB-

IQR

-RRB-

Associations

between

MTD

and

clinical

or

pathological

characteristics

were

examined

by

univariate

regression

models

Kaplan

Meier

curves

were

used

to

assess

the

risk

of

BCR

Proportional

hazards

multivariable

regression

models

were

composed

to

determine

prognostic

factors

for

BCR

SPSS

version

for

Windows

was

used

for

all

statistical

analysis

Results

Patient

and

tumor

characteristics

are

summarized

in

Table

The

age

of

the

patients

at

time

of

RP

was

years

-LRB-

IQR

years

-RRB-

and

they

had

a

median

Gleason

score

of

In

the

specimens

a

median

MTD

of

mm

-LRB-

IQR

mm

-RRB-

was

found

Patients

were

followed

for

a

median

period

of

months

-LRB-

IQR

months

-RRB-

Overall

-LRB-

-RRB-

patients

developed

BCR

after

RP

The

median

time

to

PSA

recurrence

was

months

-LRB-

IQR

-RRB-

The

overall

Kaplan

Meier

risk

of

BCR

was

-LRB-

CI

-RRB-

for

the

whole

group

For

the

high-risk

group

and

low/intermediate

risk

these

were

-LRB-

CI

-RRB-

and

-LRB-

CI

-RRB-

respectively

Totally

of

the

patients

fulfilled

the

criteria

for

high-risk

localized

PC

patients

were

low/intermediate

risk

and

patients

never

reached

non-measurable

PSA

levels

Table

and

pathological

characteristics

-LRB-

n

-RRB-

MedianIQRAge

-LRB-

years

-RRB-

period

-LRB-

months

-RRB-

PSA

-LRB-

ng/ml

-RRB-

Gleason

of

tumors

-LRB-

n

-RRB-

tumor

volume

-LRB-

-RRB-

Total

tumor

volume

-LRB-

-RRB-

Maximal

tumor

diameter

-LRB-

mm

-RRB-

Data

are

presented

as

median

and

interquartile

ranges

-LRB-

IQR

-RRB-

Associations

between

MTD

and

pathological

characteristics

are

summarized

in

Table

Overall

we

found

organ-confined

-LRB-

-RRB-

tumors

extracapsular

extended

tumors

-LRB-

-RRB-

and

tumors

invaded

into

seminal

vesicles

-LRB-

-RRB-

Half

of

all

the

patients

-LRB-

n

-RRB-

had

positive

surgical

margins

and

eight

patients

had

lymph

node

involvement

Pre-operative

PSA

levels

ranged

from

ng/ml

-LRB-

median

ng/ml

-RRB-

Kruskall

Wallis

tests

or

Mann

Whitney

U

test

revealed

that

MTD

was

significantly

associated

with

pathological

stage

-LRB-

P

-RRB-

Gleason

score

-LRB-

P

-RRB-

margin

status

-LRB-

P

-RRB-

number

of

tumors

-LRB-

P

-RRB-

and

pre-operative

PSA

levels

-LRB-

P

-RRB-

Positive

surgical

margins

were

associated

with

a

larger

MTD

compared

to

negative

surgical

margins

Single

tumors

were

also

found

to

have

a

larger

MTD

than

multiple

tumors

Extracapsular

extension

-LRB-

-RRB-

and

invasion

to

seminal

vesicles

-LRB-

-RRB-

were

both

associated

with

larger

maximal

tumor

diameters

compared

to

those

of

organ-confined

-LRB-

-RRB-

tumors

MTD

in

the

high-risk

group

was

significantly

higher

then

in

the

low/intermediate

risk

group

-LRB-

median

vs.

mm

P

-RRB-

We

also

calculated

the

correlation

coefficient

for

MTD

and

all

other

factors

We

found

that

MTD

was

significantly

correlated

to

index

TV

-LRB-

largest

tumor

-RRB-

-LRB-

r

P

-RRB-

and

total

TV

-LRB-

r

P

-RRB-

in

the

total

group

In

the

high-risk

group

these

correlations

were

weaker

In

addition

significant

correlations

with

MTD

were

found

for

Gleason

score

-LRB-

r

P

-RRB-

the

number

of

tumors

-LRB-

r

P

-RRB-

and

pre-operative

PSA

levels

-LRB-

r

P

-RRB-

Table

between

MTD

and

pathological

characteristicsNo

of

patientsMaximum

tumor

diameterMeanMedianRangeP-value

Pathological

stagea

-LRB-

-RRB-

scorea

statusb

of

tumorsb

PSAa

groupsb

High

P-values

were

assessed

by

aKruskal

Wallis

test

or

bMann

Whitney

U

test

Univariable

analyses

of

MTD

as

a

continuous

variable

revealed

that

it

is

weakly

associated

with

risk

of

BCR

-LRB-

HR

per

mm

increase

CI

P

-RRB-

In

the

high-risk

group

this

association

was

lost

-LRB-

HR

per

mm

increase

CI

P

-RRB-

In

the

total

group

TV

pre-operative

PSA

levels

pathological

stage

and

Gleason

score

were

associated

with

risk

of

BCR

as

presented

in

Table

Proportional

hazards

multivariable

regression

models

were

composed

to

determine

significant

independent

prognostic

factors

-LRB-

Table

-RRB-

Positive

surgical

margins

higher

Gleason

score

advanced

pathological

stage

and

multiple

tumors

were

the

main

prognostic

factors

for

BCR

Neither

MTD

nor

tumor

volume

turned

out

to

be

significant

in

either

group

Table

and

multivariable

analysis

of

clinical

and

pathological

characteristics

associated

with

time

to

CIPre-operative

Pathological

stage

Gleason

score

Extracapsular

Invasion

seminal

Margin

Number

of

Maximal

tumor

#Index

tumor

Total

tumor

HR

hazard

ratio

CI

confidence

interval

AHR

adjusted

hazard

ratio

P

P

Discussion

Prediction

of

outcome

after

RP

in

patients

with

localized

PC

is

important

to

tailor

follow

up

and

for

example

to

consider

adjuvant

therapy

in

patients

at

high

risk

for

recurrence

Several

studies

have

assessed

the

value

of

morphological

and

clinical

variables

in

this

respect

Tumor

stage

Gleason

score

and

pre-operative

PSA

levels

are

obvious

parameters

and

also

used

to

define

patients

at

high-risk

for

recurrence

-LSB-

-RSB-

MTD

as

easy

to

determine

surrogate

for

tumor

volume

-LSB-

-RSB-

is

another

potential

variable

considered

as

a

potential

predictor

of

BCR

In

our

study

of

patients

we

found

that

MTD

correlates

with

index

TV

total

TV

pathological

stage

Gleason

score

number

of

tumors

and

pre-operative

PSA

levels

irrespective

of

risk

classification

However

MTD

was

not

an

independent

predictor

of

BCR

in

the

total

or

in

the

high-risk

subgroup

For

the

whole

group

these

results

are

in

contrast

with

previously

reported

findings

One

of

the

first

studies

addressing

the

association

of

MTD

and

BCR

was

by

Renshaw

et

al.

-LSB-

-RSB-

In

this

study

with

patients

undergoing

RP

it

was

found

that

MTD

was

strongly

correlated

with

total

TV

In

this

small

series

a

high

MTD

was

associated

with

a

slight

increased

risk

for

BCR

-LRB-

HR

-RRB-

that

was

marginally

significant

Their

subsequent

study

was

a

larger

cohort

of

patients

The

median

MTD

was

mm

The

median

follow-up

was

months

and

of

patients

had

PSA

failure

This

study

confirmed

that

MTD

is

an

independent

predictor

of

BCR

even

after

adjustment

for

other

risk

factors

-LSB-

-RSB-

Their

next

study

by

Dvorak

et

al.

-LSB-

-RSB-

had

an

even

larger

cohort

-LRB-

patients

-RRB-

and

longer

median

follow-up

-LRB-

months

-RRB-

MTD

remained

the

same

with

a

median

of

mm

and

BCR

in

of

the

patients

Again

they

found

that

MTD

was

significantly

associated

with

time

to

BCR

-LRB-

HR

P

-RRB-

adjusted

for

pre-op

PSA

Gleason

score

and

pathological

stage

But

when

surgical

margin

status

was

added

MTD

lost

statistical

significance

-LRB-

P

-RRB-

One

important

feature

of

these

studies

is

that

the

RP

specimens

were

not

uniformly

processed

Therefore

we

have

to

be

taking

into

account

the

variation

in

evaluation

of

the

prognostic

factors

Another

difference

with

our

results

is

that

the

median

MTD

in

these

three

studies

-LRB-

mm

-RRB-

are

less

than

in

our

study

-LRB-

mm

-RRB-

This

might

be

explained

by

the

way

we

determine

our

MTD

Renshaw

et

al.

limited

their

measurements

to

the

single

focus

of

tumor

that

could

be

demonstrated

on

one

slide

-LRB-

slice-MTD

-RRB-

We

on

the

other

hand

take

the

largest

diameter

of

the

largest

tumor

after

reconstruction

-LRB-

real-MTD

-RRB-

To

see

if

we

could

explain

this

difference

we

also

measured

the

slice-MTD

in

a

part

of

our

cohort

In

consecutive

cases

from

to

we

found

a

median

slice-MTD

of

mm

and

a

median

real-MTD

of

mm

This

strongly

suggests

that

part

of

the

difference

in

MTD

is

caused

by

the

different

way

MTD

is

measured

The

difference

that

still

exists

could

be

explained

by

the

fact

that

Renshaw

et

al.

used

partially

submitted

prostates

thus

missing

part

of

the

prostates

for

evaluation

The

only

study

where

they

did

use

uniformly

processed

specimens

is

by

Eichelberger

et

al.

but

this

study

has

a

very

short

follow-up

They

analyzed

the

prognostic

value

of

MTD

in

a

cohort

of

patients

treated

with

RP

and

found

a

mean

MTD

of

mm

and

biochemical

recurrence

in

of

the

patients

-LSB-

-RSB-

In

this

study

with

a

median

follow-up

of

only

months

they

found

that

MTD

was

a

significant

predictor

of

BCR

adjusted

for

Gleason

score

and

surgical

margin

status

-LRB-

HR

P

-RRB-

In

our

study

we

found

a

median

time

to

BCR

of

months

hence

a

follow-up

of

months

seems

not

long

enough

to

investigate

BCR

Another

striking

difference

is

the

percentage

of

positive

surgical

margins

In

our

study

this

is

relatively

high

-LRB-

-RRB-

compared

to

other

studies

-LRB-

Renshaw

et

al.

and

Eichelberger

et

al.

Dvorak

et

al.

-RRB-

Our

median

BCR

rate

-LRB-

after

months

-RRB-

however

was

comparable

to

the

median

of

these

studies

-LSB-

Renshaw

-LRB-

months

-RRB-

Eichelberger

-LRB-

months

-RRB-

Dvorak

-LRB-

months

-RRB-

-RSB-

An

explanation

for

the

high

number

of

positive

surgical

margins

next

to

surgical

techniques

is

that

by

evaluating

only

partially

included

prostates

you

miss

positive

surgical

margins

The

difference

between

our

study

and

studies

like

Eichelberger

et

al

in

which

the

entire

prostate

was

histologically

examined

using

whole

mount

sections

are

less

easily

explained

but

here

the

interval

at

which

the

prostates

were

sliced

is

higher

-LRB-

mean

mm

according

to

the

used

protocol

described

by

Qian

et

al.

-LSB-

-RSB-

personal

communication

-RRB-

From

this

we

can

conclude

that

MTD

is

not

an

independent

prognostic

marker

if

surgical

resection

margins

are

accurately

documented

Finally

of

the

mentioned

studies

separately

looked

at

the

group

where

prediction

might

be

of

most

importance

the

high-risk

group

As

clearly

indicated

in

this

group

neither

MTD

nor

TV

is

of

any

significant

value

In

all

we

do

not

advice

to

use

MTD

as

a

prognostic

factor

for

BCR

since

after

proper

follow-up

and

with

adequate

pathological

techniques

it

does

not

add

anything

to

other

readily

available

prognostic

factors

Moreover

in

the

high-risk

group

TV

is

not

an

independent

prognostic

factor

at

all

Conclusions

The

results

of

our

study

suggest

that

MTD

is

positively

correlated

to

total

TV

as

can

be

expected

MTD

was

weakly

associated

with

risk

of

BCR

and

this

association

was

lost

in

the

high-risk

group

If

adjusted

for

positive

surgical

margins

higher

Gleason

score

advanced

pathological

stage

and

multiple

tumors

MTD

did

not

provide

additional

information

O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B B O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

prostate
prostatectomy
prognosis
localized
high risk