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The changing role of UK primary cancer care
Mailbox benign disease or normal controls (p < 0.005). In addition, plasma vWF was significantly higher in patients with disease of stage III or IV than in patients with stage I or II disease (p < 0.0001). More recently, we have studied the concentration of vWF in the plasma of 75 patients with colorectal cancer at various stages of disease, and compared the results with those of 88 healthy adults. Again, vWF was significantly higher in the plasma of cancer patients than in the controls (p < 0.0001). There was also a positive correlation between Duke’s staging and plasma vWF, which was even more evident following statistical adjustment for age (p < 0.0001).
Although the mechanisms involved in the elevation of plasma vWF in cancer patients are not fully understood, there is evidence that tumourdependent endothelial-cell proliferation and thrombin release, as well as the decrease in the cleavage of vWF by a protease control system observed in malignant disease may partially explain the observations mentioned above.6 Gilberto Schwartsmann, Daniel C Damin, and Israel Roisemberg Postgraduate Course in Medicine and Medical Sciences, Academic Hospital, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2350/ sala 399, CP 90035003 Porto Alegre, Brazil.
1 Nash GF, Walsh DC, Kakkar AK. The role of the coagulation system in tumour angiogenesis. Lancet Oncol 2001; 2: 608–13. 2 Dvorak HF, Sioussat TM, Brown LF, et al. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med 1991; 174: 1275–78. 3 Ruggeri ZM. von Willebrand factor. J Clin Invest 1997; 99: 559–64. 4 Pottinger BE, Read RC, Paleolog EM, et al. von Willebrand factor is an acute phase reactant in man. Thromb Res 1988; 53: 387–94. 5 Sweeney JD, Killion KM, Pruet CF, Spalding MB. von Willebrand factor in head and neck cancer. Cancer 1990; 11: 2387–89. 6 Rohsig LM, Damin DC, Castro CG, et al. von Willebrand factor antigen levels in plasma of patients with malignant breast disease. Braz J Med Biol Res 2001; 34: 1125–29.
Procaspase activation in lung carcinomas In the review article, Apoptosis: implications of basic research for clinical oncology1, the authors state, “. . . although small-cell lung-cancer cells showed high expression of BCL2 protein, they were more sensitive to spontaneous and radiation-induced apoptosis than were non-small-cell lung-cancer cells, which have low expression of this protein”. Elsewhere in the article the authors further state, “. . . cells from small-cell lung cancers lack procaspases 1, 4, 8, and 10 compared with those from nonsmall-cell lung carcinomas. The significance of these findings is unclear, because small-cell lung cancers are generally more sensitive to chemotherapy-triggered apoptosis.” A simple hypothesis, which would explain these two observations, is that uncleaved procaspase
molecules act as inhibitors of selfcleavage activation of their target caspases. It is known that procaspases are capable of self-cleavage, yet it is clear that, were this to occur at anything but a minimal background rate, the consequence would be activation of the apoptotic cascade leading to cell death – spontaneous apoptosis. A potential protective mechanism would be for uncleaved procaspases to inhibit self-cleavage of downstream procaspases, possibly by binding inertly to the cleavage sites of these procaspases and so blocking access for self-activation. In contrast, activated caspases would both bind and cleave their target procaspases. In this model, the increased BCL2 protein expression of small-cell lungcancer cells, far from conferring protection against external triggers of
apoptosis, would represent the minimal amount required to prevent unstimulated apoptosis in cells lacking procaspase inhibitory activity. If confirmed, this model suggests that, in malignant cells with abnormal procaspase populations, inhibition of additional procaspases might render the cell exquisitely sensitive to therapy-induced apoptosis. Even in malignant tumours with apparently normal procaspase synthesis, a blockade of procaspase protection might render chemo- and radioresistant tumours vulnerable. Kenneth Campbell Clinical Information Officer, Leukaemia Research Fund, 43 Great Ormond Street, London, WC1N 3JJ, UK. 1 Tamm I, Schriever F, Dorken, B. Apoptosis: implications of basic research for clinical oncology. Lancet Oncol 2001; 2: 33–42.
The changing role of UK primary cancer care Primary care oncology is as much about primary care medicine as it is about oncology. The problem is that many of the current initiatives affecting primary care are being driven by those who have no experience, or little understanding, of life as a primary care physician. In such a climate there is a risk of considerable adverse consequences to THE LANCET Oncology Vol 2 December 2001
both the profession and to our patients. Primary care oncology can be divided into two major parts: those things that primary care clinicians are doing already, and those things that they could potentially take on. To many, cancer recognition is the prime example of the former and is an area in which significant improvements
could be made. Patients with cancer invariably present with common symptoms such as persistent cough or non-specific abdominal pain, although very few patients with such problems who are examined by a primary care physician turn out to have malignant disease. However, medical research has not addressed, in any meaningful manner, which 717
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Mailbox symptoms are important in primary care, which symptoms are a reliable indicator of malignant disease, which symptoms are not useful, and which symptoms will rule out disease. 1,2 The implication within the National Health Service (NHS) Cancer Plan3 is that the issue of cancer recognition by a primary care physician has been resolved by the publication of evidence-deficient and secondary-care-dominated consensus of referral guidelines.3 However, this issue has not been effectively addressed, and it is misleading and dangerous to promote these guidelines in an electronic format. The NHS Cancer Plan3 also seeks to encourage closer involvement of primary care clinicians throughout the whole cancer-care journey in relation to issues such as cancer follow-up and shared care. However, in seeking to improve overall cancer services and involve primary care in such developments, extreme care must be taken to ensure that all the consequences have been fully
considered. There is a need to be confident about both the applicability and the validity of any published evidence favouring such service reconfigurations, as well as having a realistic understanding of the capacity and commitment within primary care. Furthermore, any changes must be carefully evaluated to make sure that they do not harm the patients (and, ideally, are actually of benefit!). I warmly welcome the November editorial4 and I hope it will encourage a wider debate, in which both policymakers and primary care researchers begin to listen to primary care clinicians. As a primary care physician myself, I wish to play my part in enhancing cancer survival in the UK,5 but, to do this, I first need better evidence to help me to address the many common diagnostic dilemmas that confront me on a daily basis. For example, I want to be able to deliver my patients with suspected colorectal cancer to my secondarycare colleagues at an earlier Duke’s
stage so that they can be cured; the problem is that no one can tell me what the features of early stage disease in a low prevalence population are.6 Nick Summerton The Surgery, Manlake Avenue, Winterton, Scunthorpe, DN15 9TA, UK. 1 Owen P. Clinical practice and medical research: bridging the divide between the two cultures. Brit J Gen Pract 1995; 45: 557–60. 2 iedekerken BMJ, Hoogendam A, Buntinx F, et al. Prolonged cough and lung cancer: the need for more general practice research to inform clinical decision making. Br J Gen Pract 1997; 47: 505. 3 UK Department of Health. The NHS cancer plan: referral guidelines for suspected cancer. www.doh.gov.uk/cancer, accessed Nov 2001. 4 The Lancet Oncology. The changing role of UK primary cancer care. Lancet Oncol 2001; 2: 649. 5 Berrino F, Capocaccia R, Esteve J, et al (Eds). Survival for cancer patients in Europe; the Eurocare II study. Lyon: International Agency for Research on Cancer, 1999. 6 Summerton N. Diagnosis and general practice. Brit J Gen Pract 2000; 50: 995–1000.
If you would like to respond to an article in THE LANCET Oncology, or to share your views on a current topic of interest or concern within oncology, please do email your letter, together with full contact details, to [email protected] or fax it through on +44 (0)20 7611 4466 or post it to THE LANCET Oncology, 84 Theobald’s Road, London WC1X 8RR
718
THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Although the mechanisms involved in the elevation of plasma vWF in cancer patients are not fully understood, there is evidence that tumourdependent endothelial-cell proliferation and thrombin release, as well as the decrease in the cleavage of vWF by a protease control system observed in malignant disease may partially explain the observations mentioned above.6 Gilberto Schwartsmann, Daniel C Damin, and Israel Roisemberg Postgraduate Course in Medicine and Medical Sciences, Academic Hospital, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2350/ sala 399, CP 90035003 Porto Alegre, Brazil.
1 Nash GF, Walsh DC, Kakkar AK. The role of the coagulation system in tumour angiogenesis. Lancet Oncol 2001; 2: 608–13. 2 Dvorak HF, Sioussat TM, Brown LF, et al. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med 1991; 174: 1275–78. 3 Ruggeri ZM. von Willebrand factor. J Clin Invest 1997; 99: 559–64. 4 Pottinger BE, Read RC, Paleolog EM, et al. von Willebrand factor is an acute phase reactant in man. Thromb Res 1988; 53: 387–94. 5 Sweeney JD, Killion KM, Pruet CF, Spalding MB. von Willebrand factor in head and neck cancer. Cancer 1990; 11: 2387–89. 6 Rohsig LM, Damin DC, Castro CG, et al. von Willebrand factor antigen levels in plasma of patients with malignant breast disease. Braz J Med Biol Res 2001; 34: 1125–29.
Procaspase activation in lung carcinomas In the review article, Apoptosis: implications of basic research for clinical oncology1, the authors state, “. . . although small-cell lung-cancer cells showed high expression of BCL2 protein, they were more sensitive to spontaneous and radiation-induced apoptosis than were non-small-cell lung-cancer cells, which have low expression of this protein”. Elsewhere in the article the authors further state, “. . . cells from small-cell lung cancers lack procaspases 1, 4, 8, and 10 compared with those from nonsmall-cell lung carcinomas. The significance of these findings is unclear, because small-cell lung cancers are generally more sensitive to chemotherapy-triggered apoptosis.” A simple hypothesis, which would explain these two observations, is that uncleaved procaspase
molecules act as inhibitors of selfcleavage activation of their target caspases. It is known that procaspases are capable of self-cleavage, yet it is clear that, were this to occur at anything but a minimal background rate, the consequence would be activation of the apoptotic cascade leading to cell death – spontaneous apoptosis. A potential protective mechanism would be for uncleaved procaspases to inhibit self-cleavage of downstream procaspases, possibly by binding inertly to the cleavage sites of these procaspases and so blocking access for self-activation. In contrast, activated caspases would both bind and cleave their target procaspases. In this model, the increased BCL2 protein expression of small-cell lungcancer cells, far from conferring protection against external triggers of
apoptosis, would represent the minimal amount required to prevent unstimulated apoptosis in cells lacking procaspase inhibitory activity. If confirmed, this model suggests that, in malignant cells with abnormal procaspase populations, inhibition of additional procaspases might render the cell exquisitely sensitive to therapy-induced apoptosis. Even in malignant tumours with apparently normal procaspase synthesis, a blockade of procaspase protection might render chemo- and radioresistant tumours vulnerable. Kenneth Campbell Clinical Information Officer, Leukaemia Research Fund, 43 Great Ormond Street, London, WC1N 3JJ, UK. 1 Tamm I, Schriever F, Dorken, B. Apoptosis: implications of basic research for clinical oncology. Lancet Oncol 2001; 2: 33–42.
The changing role of UK primary cancer care Primary care oncology is as much about primary care medicine as it is about oncology. The problem is that many of the current initiatives affecting primary care are being driven by those who have no experience, or little understanding, of life as a primary care physician. In such a climate there is a risk of considerable adverse consequences to THE LANCET Oncology Vol 2 December 2001
both the profession and to our patients. Primary care oncology can be divided into two major parts: those things that primary care clinicians are doing already, and those things that they could potentially take on. To many, cancer recognition is the prime example of the former and is an area in which significant improvements
could be made. Patients with cancer invariably present with common symptoms such as persistent cough or non-specific abdominal pain, although very few patients with such problems who are examined by a primary care physician turn out to have malignant disease. However, medical research has not addressed, in any meaningful manner, which 717
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Mailbox symptoms are important in primary care, which symptoms are a reliable indicator of malignant disease, which symptoms are not useful, and which symptoms will rule out disease. 1,2 The implication within the National Health Service (NHS) Cancer Plan3 is that the issue of cancer recognition by a primary care physician has been resolved by the publication of evidence-deficient and secondary-care-dominated consensus of referral guidelines.3 However, this issue has not been effectively addressed, and it is misleading and dangerous to promote these guidelines in an electronic format. The NHS Cancer Plan3 also seeks to encourage closer involvement of primary care clinicians throughout the whole cancer-care journey in relation to issues such as cancer follow-up and shared care. However, in seeking to improve overall cancer services and involve primary care in such developments, extreme care must be taken to ensure that all the consequences have been fully
considered. There is a need to be confident about both the applicability and the validity of any published evidence favouring such service reconfigurations, as well as having a realistic understanding of the capacity and commitment within primary care. Furthermore, any changes must be carefully evaluated to make sure that they do not harm the patients (and, ideally, are actually of benefit!). I warmly welcome the November editorial4 and I hope it will encourage a wider debate, in which both policymakers and primary care researchers begin to listen to primary care clinicians. As a primary care physician myself, I wish to play my part in enhancing cancer survival in the UK,5 but, to do this, I first need better evidence to help me to address the many common diagnostic dilemmas that confront me on a daily basis. For example, I want to be able to deliver my patients with suspected colorectal cancer to my secondarycare colleagues at an earlier Duke’s
stage so that they can be cured; the problem is that no one can tell me what the features of early stage disease in a low prevalence population are.6 Nick Summerton The Surgery, Manlake Avenue, Winterton, Scunthorpe, DN15 9TA, UK. 1 Owen P. Clinical practice and medical research: bridging the divide between the two cultures. Brit J Gen Pract 1995; 45: 557–60. 2 iedekerken BMJ, Hoogendam A, Buntinx F, et al. Prolonged cough and lung cancer: the need for more general practice research to inform clinical decision making. Br J Gen Pract 1997; 47: 505. 3 UK Department of Health. The NHS cancer plan: referral guidelines for suspected cancer. www.doh.gov.uk/cancer, accessed Nov 2001. 4 The Lancet Oncology. The changing role of UK primary cancer care. Lancet Oncol 2001; 2: 649. 5 Berrino F, Capocaccia R, Esteve J, et al (Eds). Survival for cancer patients in Europe; the Eurocare II study. Lyon: International Agency for Research on Cancer, 1999. 6 Summerton N. Diagnosis and general practice. Brit J Gen Pract 2000; 50: 995–1000.
If you would like to respond to an article in THE LANCET Oncology, or to share your views on a current topic of interest or concern within oncology, please do email your letter, together with full contact details, to [email protected] or fax it through on +44 (0)20 7611 4466 or post it to THE LANCET Oncology, 84 Theobald’s Road, London WC1X 8RR
718
THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.